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1. Type I IFN controls chikungunya virus via its action on nonhematopoietic cells

Author: Stephen Higgs, Marco Colonna, Alain Michault, Fernando Arenzana-Seisdedos, Thérèse Couderc, Nicolas Gangneux, Marion Sourisseau, Matthew L. Albert, Anton Kraxner, Olivier Schwartz, Lucie Peduto, Fabrice Chrétien, Marc Lecuit, Florence Guivel-Benhassine, Jürg Tschopp, Clémentine Schilte, Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Microorganismes et Barrières de l'Hôte (Equipe avenir), Cellules Souches et Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité, Institute of Biochemistry, Université de Lausanne (UNIL)-BIL Biomedical Research Center, The University of Texas Medical Branch (UTMB), Service de microbiologie, Groupe Hospitalier Sud-CHR La réunion, Pathogénie Virale Moléculaire, Virologie, Centre National de la Recherche Scientifique (CNRS), Department of Immunology, Washington University, Développement des Tissus Lymphoïdes, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), This work was supported in part by grants from L'Agence Nationale de la Récherche and the Institut Pasteur Programmes Traversaux de Recherche (O. Schwartz, M. Lecuit, and M.L. Albert) and La Ligue Nationale Contre le Cancer, The EURYI Scheme, and European Science Foundation (M.L. Albert)., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL)-BIL Biomedical Research Center, Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Gau, Mireille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe avenir Microorganismes et Barrières de l'Hôte, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Lausanne ( UNIL ) -BIL Biomedical Research Center, The University of Texas Medical Branch ( UTMB ), Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: Immunology, Receptor, Interferon alpha-beta, medicine.disease_cause, Antibodies, Viral, Virus, Article, 03 medical and health sciences, Mice, Immune system, Interferon, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Adaptor Proteins, Signal Transducing/immunology, Adaptor Proteins, Signal Transducing/metabolism, Alphavirus Infections/blood, Alphavirus Infections/immunology, Animals, Antibodies, Neutralizing/blood, Antibodies, Neutralizing/immunology, Antibodies, Viral/blood, Antibodies, Viral/immunology, Blood Cells/immunology, Blood Cells/metabolism, Chikungunya virus, Humans, Interferon Type I/immunology, Mice, Knockout, RNA, Viral, Receptor, Interferon alpha-beta/immunology, Receptor, Interferon alpha-beta/metabolism, Signal Transduction, Viral Load, medicine, Immunology and Allergy, Chikungunya, Alphavirus infection, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Adaptor Proteins, Signal Transducing, 0303 health sciences, Blood Cells, biology, 030306 microbiology, Alphavirus Infections, virus diseases, medicine.disease, Virology, Antibodies, Neutralizing, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Interferon Type I, biology.protein, Antibody, Viral load, Interferon type I, medicine.drug
Abstract: International audience; Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-alpha/beta receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR(-/-)-->WT bone marrow chimeras are capable of clearing the infection, whereas WT-->IFNAR(-/-) chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV.
Published: 2010
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2. Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial

Author: Natalie Baecker, Jean-Pol Frippiat, Katharina Austermann, Peter Stehle, Scott M. Smith, Rolf Fimmers, Martina Heer, Sara R. Zwart, Rheinische Friedrich-Wilhelms-Universität Bonn, The University of Texas Medical Branch (UTMB), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), NASA Johnson Space Center (JSC), and NASA
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medicine (miscellaneous), Parathyroid hormone, 030209 endocrinology & metabolism, Antioxidants, Collagen Type I, Bone resorption, Bone remodeling, Head-Down Tilt, Selenium, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, Vitamin E, Single-Blind Method, Bone Resorption, 2. Zero hunger, Calcium metabolism, 030109 nutrition & dietetics, Nutrition and Dietetics, biology, business.industry, Polyphenols, Urinary calcium, 3. Good health, Endocrinology, Dietary Supplements, Osteocalcin, biology.protein, Calcium, Bone Remodeling, business, Bed Rest, Biomarkers, Type I collagen
Abstract: International audience; Background Immobilization and related oxidative stress are associated with bone loss. Antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate these negative effects on bone metabolism through scavenging of free radicals. Objectives We hypothesized that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR) would reduce bone resorption and increase bone formation compared to nonsupplemented controls. Methods This exploratory randomized, controlled, single-blind intervention study conducted in a parallel design included 20 healthy male volunteers (age, 34 ± 8 years; weight, 74 ± 6 kg). The study consisted of a 14-day adaptation phase [baseline data collection (BDC)], followed by 60 days of HDBR and a 14-day recovery period (R). In the antioxidant group, volunteers received an antioxidant cocktail (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E, and 80 μg/d selenium) with their daily meals. In the control group, volunteers received no supplement. Based on their body weight, all volunteers received an individually tailored and strictly controlled diet, consistent with DRIs. We analyzed biomarkers of calcium homeostasis, bone formation, and bone resorption during BDC, HDBR, and R, as well as for 30 days after the end of HDBR. Data were analyzed by linear mixed models. Results The antioxidant supplement did not affect serum calcium, parathyroid hormone, urinary C-telopeptide of type I collagen (CTX), urinary N-telopeptide of type I collagen, serum β–C-telopeptide of type I collagen (β-CTX), bone alkaline phosphatase, aminoterminal propeptide of type I collagen, osteocalcin, or urinary calcium excretion. In both groups, typical bed rest–related changes were observed. Conclusions Supplementation of an antioxidant cocktail to a diet matching the DRIs did not affect bone resorption or formation during 60 days of HDBR in healthy young men. This trial was registered at clinicaltrials.gov as NCT03594799.
Published: 2021
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3. Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice

Author: Stanley M. Lemon, Emilie Mérour, Hervé Lerat, Hélène L. Kammoun, Celine Callens, Martin R. Higgs, Jean-Michel Pawlotsky, Fabienne Foufelle, Isabelle Hainault, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Human Infections and Immunity, The University of Texas Medical Branch (UTMB), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), The University of Texas Medical Branch ( UTMB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Guellaen, Georges
Subjects: Male, medicine.medical_specialty, Transgene, Blotting, Western, Mice, Transgenic, Lipids and Lipoproteins: Metabolism, Regulation, and Signaling, Hepacivirus, Biology, Endoplasmic Reticulum, Biochemistry, Mice, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, Secretion, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Triglycerides, 030304 developmental biology, Cytopathic effect, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Lipogenesis, Fatty liver, virus diseases, Lipid metabolism, Cell Biology, medicine.disease, Hepatitis C, Virology, digestive system diseases, 3. Good health, Fatty Liver, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Liver, Unfolded protein response, 030211 gastroenterology & hepatology, Steatosis, Sterol Regulatory Element Binding Protein 1
Abstract: This research was originally published in The Journal of Biological Chemistry. © the American Society for Biochemistry and Molecular Biology; International audience; Chronic hepatitis C virus (HCV) infection is associated with altered lipid metabolism and hepatocellular steatosis. Virus-induced steatosis is a cytopathic effect of HCV replication. The goal of this study was to examine the mechanisms underlying HCV-induced lipid metabolic defects in a transgenic mouse model expressing the full HCV protein repertoire at levels corresponding to natural human infection. In this model, expression of the HCV full-length open reading frame was associated with hepatocellular steatosis and reduced plasma triglyceride levels. Triglyceride secretion was impaired, whereas lipogenesis was activated. Increased lipogenic enzyme transcription was observed, resulting from maturational activation and nuclear translocation of sterol regulatory element-binding protein 1c (SREBP1c). However, endoplasmic reticulum (ER) stress markers were expressed at similar levels in both HCV transgenic mice and their wild type counterparts, suggesting that SREBP1c proteolytic cleavage in the presence of HCV proteins was independent of ER stress. In conclusion, transgenic mice expressing the HCV full-length polyprotein at low levels have decreased plasma triglyceride levels and develop hepatocellular steatosis in the same way as HCV-infected patients. In these mice, SREBP1c activation by one or several HCV proteins induces de novo triglyceride synthesis via the lipogenic pathway, in a manner independent of ER stress, whereas triglyceride secretion is simultaneously reduced.
Published: 2009
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4. Excess all-cause mortality and COVID-19-related mortality:a temporal analysis in 22 countries, from January until August 2020

Author: Oscar Dario Martin Garzon, Fabrizio Stracci, Levan Kandelaki, Jose M. Rodriguez-Llanes, Julia A Critchley, Eva S. Schernhammer, Giuseppe Ambrosio, Neil Mehta, Cathy Bennett, Ourania Kolokotroni, Gleb Denissov, Qian Huang, Lucy Goldsmith, Maider Pagola Ugarte, Inbar Zucker, Jackeline Christiane Pinto Lobato, Petra Klepac, Constantina Constantinou, Alexandros Heraclides, Nolwenn Le Meur, Annalisa Quattrocchi, Kristi Rüütel, Antonio José Leal Costa, Claudia Zimmermann, Ángel Fernández Camporro, Ekaterina Bogatyreva, John Gabel, Pedro Arcos González, Christiana A. Demetriou, Ana Paula Semedo-Aguiar, Ivan Erzen, Laust Hvas Mortensen, Souzana Achilleos, Joan O'Donnell, Nicoletta Nicolaou, Zalman Kaufman, Terje P. Hagen, Shorena Tsiklauri, Gloria Ramírez, Nataliia Pidmurniak, Antonis Polemitis, Olesia Verstiuk, Ngibo Mubeta Fernandes, Ajay Oza, Bo Burström, Andreas Charalambous, University of Cyprus [Nicosia], European Commission - Joint Research Centre [Ispra] (JRC), Deakin University [Burwood], Medizinische Universität Wien = Medical University of Vienna, University of Copenhagen = Københavns Universitet (KU), St George’s University Hospitals, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Tel Aviv University [Tel Aviv], Università degli Studi di Perugia (UNIPG), University of Oslo (UiO), University of Oviedo, Karolinska Institutet [Stockholm], Bogomolets national medical university, University of South Carolina [Columbia], The University of Texas Medical Branch (UTMB), This work was supported by the University of Nicosia Medical School (internal funding), University of Cyprus [Nicosia] (UCY), University of Copenhagen = Københavns Universitet (UCPH), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Tel Aviv University (TAU), and Università degli Studi di Perugia = University of Perugia (UNIPG)
Subjects: 0301 basic medicine, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Northern ireland, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, AcademicSubjects/MED00860, 030212 general & internal medicine, Excess mortality, business.industry, SARS-CoV-2, Mortality rate, pandemic, COVID-19, General Medicine, Seasonality, medicine.disease, mortality, infection control, 3. Good health, 030104 developmental biology, Original Article, business, All cause mortality, Demography
Abstract: This work was supported by the University of Nicosia Medical School (internal funding)., Achilleos S, Quattrocchi A, Gabel J, Heraclides A, Kolokotroni O, Constantinou C, Pagola Ugarte M, Nicolaou N, Rodriguez-Llanes JM, Bennett CM, Bogatyreva E, Schernhammer E, Zimmermann C, Costa AJL, Lobato JCP, Fernandes NM, Semedo-Aguiar AP, Jaramillo Ramirez GI, Martin Garzon OD, Mortensen LH, Critchley JA, Goldsmith LP, Denissov G, Rüütel K, Le Meur N, Kandelaki L, Tsiklauri S, O'Donnell J, Oza A, Kaufman Z, Zucker I, Ambrosio G, Stracci F, Hagen TP, Erzen I, Klepac P, Arcos González P, Fernández Camporro Á, Burström B, Pidmurniak N, Verstiuk O, Huang Q, Mehta NK, Polemitis A, Charalambous A, Demetriou CA.
Published: 2022
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5. Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Author: Geoffroy Lorin de la Grandmaison, Antonio Cibelli, David C. Spray, Juan E. Tichauer, Jean Dubuisson, Arielle Rosenberg, Ross H. Luu, Sandrine Belouzard, Eliana Scemes, Elisabeth Cramer-Bordé, Morgane Bomsel, Djillali Annane, Maximiliano Rovegno, Andrea Cottignies-Calamarte, Silvana Valdebenito, Eliseo A. Eugenin, Calude Capron, [Institut Cochin] Departement Infection, immunité, inflammation, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), The University of Texas Medical Branch (UTMB), New York Medical College (NYMC), Albert Einstein College of Medicine [New York], Pontificia Universidad Católica de Chile (UC), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Ambroise Paré [AP-HP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Service médical des soins intensifs [CHU Raymond Poincaré], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The authors acknowledge financial support from the National Institutes of Health grant: MH096625/MH128082, The National Institute of Neurological Disorders and Stroke, NS105584, and UTMB internal funding (to E.A.E).Also, funding from the Flash COVID fund from both ANR and Fondation pour la Recherche Medicale (ANR-20-COVI-000 and AO2020- MUCOLUNG-ANR Flash COVID-19 - FRM) was provided to M.B., ANR-20-COVI-0024,MUCOLUNG,Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses(2020), Bomsel, Morgane, and Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses - - MUCOLUNG2020 - ANR-20-COVI-0024 - COVID-19 - VALID
Subjects: Cell biology, Human coronavirus 229E, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, viruses, Connexin, Endocytosis, medicine.disease_cause, Article, lung, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Multiplicity of infection, Virology, medicine, purinergic, education, Furin, Molecular physiology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Coronavirus, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Chemistry, COVID-19, virus diseases, Pannexin, biology.organism_classification, respiratory tract diseases, 3. Good health, ATP, Allograft inflammatory factor 1, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030217 neurology & neurosurgery
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE2, and IL-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE2, and IL-1β levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy., Graphical abstract, Cell biology; Molecular physiology; Virology
Published: 2021
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6. Rational design of universal immunotherapy for TfR1-tropic arenaviruses

Author: Thomas W. Geisbert, Vered Padler-Karavani, Sylvain Baize, Hadas Cohen-Dvashi, Ron Amon, Krystle N. Agans, Aliza Borenstein-Katz, Ron Diskin, Robert W. Cross, Mathieu Mateo, Weizmann Institute of Science [Rehovot, Israël], Tel Aviv University (TAU), The University of Texas Medical Branch (UTMB), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), BSL-4 experiments using MACV were supported by the Pasteur-Weizmann joint research program collaborative research grant S-CR18069-02 to M.M. and R.D. BSL-4 operations of the Galveston National Laboratory and Department of Microbiology and Immunology are supported by NIAID/NIH Grant No. UC7AI094660 to T.W.G. The lab of R.D. is supported by research grants from the Enoch Foundation, from the Abramson Family Center for Young Scientists, from Ms. Rudolfine Steindling, and from the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grants no. 1775/12 and 682/16)., Tel Aviv University [Tel Aviv], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), and Bodescot, Myriam
Subjects: 0301 basic medicine, New World Arenavirus, Viral protein, medicine.medical_treatment, Science, viruses, General Physics and Astronomy, Transferrin receptor, Biologics, Biology, Antibodies, Viral, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Virology, Receptors, Transferrin, medicine, Arenaviridae Infections, Humans, lcsh:Science, X-ray crystallography, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multidisciplinary, Transmission (medicine), Rational design, virus diseases, Arenavirus, General Chemistry, Immunotherapy, Antibodies, Neutralizing, Arenaviruses, 3. Good health, Hemorrhagic Fevers, 030104 developmental biology, Drug Design, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Biological warfare, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Receptors, Virus, lcsh:Q, 030217 neurology & neurosurgery
Abstract: Certain arenaviruses that circulate in rodent populations can cause life-threatening hemorrhagic fevers when they infect humans. Due to their efficient transmission, arenaviruses pose a severe risk for outbreaks and might be exploited as biological weapons. Effective countermeasures against these viruses are highly desired. Ideally, a single remedy would be effective against many or even all the pathogenic viruses in this family. However, despite the fact that all pathogenic arenaviruses from South America utilize transferrin receptor 1 (TfR1) as a cellular receptor, their viral glycoproteins are highly diversified, impeding efforts to isolate cross-neutralizing antibodies. Here we address this problem using a rational design approach to target TfR1-tropic arenaviruses with high potency and breadth. The pan-reactive molecule is highly effective against all arenaviruses that were tested, offering a universal therapeutic approach. Our design scheme avoids the shortcomings of previous immunoadhesins and can be used to combat other zoonotic pathogens., New World arenaviruses utilize the cellular transferrin receptor 1 (TfR1) to enter host cells. Here, the authors develop a TfR1-mimetic immunoadhesin, Arenacept, that targets viral spike complexes and exerts effective pan-reactive neutralization against pathogenic mammarenaviruses.
Published: 2020
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7. Antiviral activity of oleandrin and a defined extract of Nerium oleander against SARS-CoV-2

Author: Rick Matos, Divya Mirchandani, Scott C. Weaver, Diana Fernández, Jordi B. Torrelles, Varun Dwivedi, Jennifer Delgado, Nathen E. Bopp, Kenneth S. Plante, Vinay Shivanna, Patricia V. Aguilar, Jun Gyu Park, Luis Martinez-Sobrido, Jessica A. Plante, Paula Pino Tamayo, Robert A. Newman, K. Jagannadha Sastry, The University of Texas Medical Branch (UTMB), World Reference Center for Emerging Viruses and Arboviruses (WRCEVA), Institute for Human Infections and Immunity and Department of Pathology, Texas Biomedical Research Institute [San Antonio, TX], Innovar LLC, Phoenix Biotechnology, Inc., The University of Texas M.D. Anderson Cancer Center [Houston], and This research was supported in part by NIH grant R24 AI120942 to SCW. We thank Natalie Thornburg (Centers 305 for Disease Control and Prevention, Atlanta, GA, USA) and the World Reference Center for Emerging Viruses and Arboviruses for providing the SARS-CoV-2 USA_WA1/2020 isolate. Research was also supported by Phoenix Biotechnology, Inc. Experimental design, conduct of the experiments, and interpretation of the data were the independent products of scientists at University of Texas Medical Branch (Galveston) and Texas Biomedical Research Institute with consulting comments from R. A. Newman, PhD, and K. Jagannadha Sastry, PhD. The authors thank Bev Newman, M.S., R.N. for graphic art support.
Subjects: 0301 basic medicine, Oleandrin, NP, nucleocapsid protein, LDH, lactic dehydrogenase, [SDV]Life Sciences [q-bio], DPI, day post infection, Pharmacology, DMSO, dimethyl sulfoxide, medicine.disease_cause, law.invention, chemistry.chemical_compound, 0302 clinical medicine, HTLV-1, human T-lymphotropic virus, law, Cricetinae, Chlorocebus aethiops, Mab, monoclonal antibody, Antiviral activity, Coronavirus, General Medicine, 3. Good health, HIV, human immunodeficiency virus, Cardenolides, Titer, CPE, cytopathic effect, Reduced infectivity, 030220 oncology & carcinogenesis, BDNF, brain-derived neurotrophic factor, EC50, half maximal effective concentration, Female, Original Article, ATP, adenosine triphosphate, ALT, alanine transaminase, Genome, Viral, RM1-950, Antiviral Agents, Virus, MERS, middle east respiratory syndrome, 03 medical and health sciences, FBS, fetal bovine serum, In vivo, medicine, DPBS, Dulbecco’s phosphate-buffered saline, Animals, Nerium, SARS, severe acute respiratory syndrome, Vero Cells, EC50, ELISA, enzyme-linked immunoassay, ALP, alkaline phosphatase, Plant Extracts, business.industry, SARS-CoV-2, COVID-19, Nrf-2, nuclear factor erythroid 2-related factor 2, Nerium oleander, COVID-19 Drug Treatment, 030104 developmental biology, chemistry, qRT-PCR, real-time quantitative polymerase chain reaction, Vero cell, RNA, ribonucleic acid, H&E, hematoxylin and eosin, BSA, bovine serum albumin, Therapeutics. Pharmacology, business, Phytotherapy, PFU, plaque-forming unit
Abstract: International audience; With continued expansion of the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), both antiviral drugs as well as effective vaccines are desperately needed to treat patients at high risk of life-threatening disease. Here, we present in vitro evidence for significant inhibition of SARS-CoV-2 by oleandrin and a defined extract of N. oleander (designated as PBI-06150). Using Vero cells, we found that prophylactic (pre-infection) oleandrin (as either the pure compound or as the active principal ingredient in PBI-06150) administration at concentrations as low as 0.05g/ml exhibited potent antiviral activity against SARS-CoV-2, with an 800-fold reduction in virus production, and a 0.1g/ml concentration resulted in a greater than 3000-fold reduction in infectious virus production. The half maximal effective concentration (EC50) values were 11.98ng/ml when virus output was measured at 24h post-infection, and 7.07ng/ml measured at 48h post-infection. Therapeutic (post-infection) treatment up to 24h after SARS-CoV-2 infection of Vero cells also reduced viral titers, with 0.1g/ml and 0.05g/ml concentrations causing greater than 100-fold reduction as measured at 48h, and the 0.05g/ml concentration resulting in a 78-fold reduction. Concentrations of oleandrin up to 10g/ml were well tolerated in Vero cells. We also present in vivo evidence of the safety and efficacy of defined N. oleander extract (PBI-06150), which was administered to golden Syrian hamsters in a preparation containing as high as 130g/ml of oleandrin. In comparison to administration of control vehicle, PBI-06150 provided a statistically significant reduction of the viral titer in the nasal turbinates (nasal conchae). The potent prophylactic and therapeutic antiviral activities demonstrated here, together with initial evidence of its safety and efficacy in a relevant hamster model of COVID-19, support the further development of oleandrin and/or defined extracts containing this molecule for the treatment of SARS-CoV-2 and associated COVID-19 disease and potentially also for reduction of virus spread by persons diagnosed early after infection.
Published: 2021
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8. Resurgence of Ebola Virus in 2021 in Guinea Suggests a New Paradigm for Outbreaks

Author: Fodé B. Sako, Jacob Camara, Amadou A. Sall, Ariane Düx, Giuditta Annibaldis, Meike Pahlmann, Abdoulaye Toure, Ousmane Faye, Mamadou Condé, Haby Diallo, Steven T. Pullan, Amadou Sidibe, Moriba Povogui, Fara Raymond Koundouno, Christophe Peyrefitte, Liana E. Kafetzopoulou, Alpha Kabinet Keita, Saa L. Millimono, Mandiou Diakite, Ahmadou Doré, Karla Pietro, N'. Faly Magassouba, Fabian H. Leendertz, Nicole Vidal, Stephan Günther, Anke Thielebein, Julia Hinzmann, Dembo Diakite, Ahidjo Ayouba, Cheikh Loucoubar, Kaka Kourouma, Martin Faye, Philippe Lemey, Moussa Moïse Diagne, Mamadou D. Barry, Fodé Y. Soumah, Annick Renevey, Georges Ki-Zerbo, Kékoura Ifono, Andrew Rambaut, Abdoul K. Soumah, Miles W. Carroll, Mamadou S. Bah, Joseph Akoi Bore, Ibrahima Camara, Mamadou S. Sow, Sébastien Calvignac-Spencer, Fodé A. Traore, Sophie Duraffour, Assaïtou Bah, John T. McCrone, Nathalie J. Vielle, Joshua Quick, Noël Tordo, Moussa Baldé, Mamadou Diop, Youssouf Sidibé, Martine Peeters, Madeleine Kourouma, Sakoba Keita, Mamadou B. Keita, Frédéric Le Marcis, Cé D. Saouromou, Anais Legand, Amadou Diallo, Pierre Formenty, Almudena Mari-Saez, Michael R. Wiley, Karifa Kourouma, Eric Delaporte, Barré Soropogui, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Robert Koch Institute [Berlin] (RKI), German Center for Infection Research - Partner Site Hamburg-Lübeck-Borstel-Riems, German Centre for Infection Research (DZIF), Centre de Recherche et de Formation en Infectiologie de Guinée [Conakry, Guinée] (CERFIG), Triangle : action, discours, pensée politique et économique (TRIANGLE), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Hôpital National Donka, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Epidemiology of Highly Pathogenic Microorganisms, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), CEA Tech Grand-Est (DGDE), CEA Tech en régions (CEA-TECH-Reg), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de Santé Publique [Conakry, Guinée] (INSP), Ministère de la Santé [Conakry, Guinea], Laboratoire de Physique de l'Atmosphère et de l'Océan Siméon Fongang (LPAO-SF), École Supérieure Polytechnique de Dakar (ESP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Public Health England, University of Birmingham [Birmingham], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organization [Geneva], The University of Texas Medical Branch (UTMB), University of Nebraska Medical Center, University of Nebraska System, Institut Pasteur de Guinée, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), University of Edinburgh, Division Prévention et Lutte contre la Maladie, Ministère de la Santé et de l’Hygiène Publique, Ecole Nationale Superieure de Lyon, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Infectious and Tropical Diseases Department [Montpellier], Institut de Recherche pour le Développement (IRD)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft, ANR-16-IDEX-0006,MUSE,MUSE(2016), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), University of Oxford [Oxford], Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CEA Tech Alsace Champagne-Ardenne Lorraine, École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Michel de l'Hospital : laboratoire de recherche en sciences juridiques et politiques (CMH ), and Université Clermont Auvergne (UCA)
Subjects: Male, Zaire ebolavirus, Time Factors, viruses, Disease, Biology, medicine.disease_cause, Disease cluster, Models, Biological, Viral Zoonoses, Virus, Disease Outbreaks, 03 medical and health sciences, Ebola virus, 0302 clinical medicine, medicine, Animals, Humans, Survivors, 030212 general & internal medicine, Clade, Phylogeny, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Transmission (medicine), Guinea-2021, High-Throughput Nucleotide Sequencing, Outbreak, Hemorrhagic Fever, Ebola, [SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, Ebolavirus, Virology, 3. Good health, Democratic Republic of the Congo, Female, Persistent Infection, epidemiology, Guinea, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak—between 14 February and 19 June 2021—near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization. The viral lineage responsible for the February 2021 outbreak of Ebola virus disease in Guinea is nested within a clade that predominantly consists of genomes sampled during the 2013–2016 epidemic, suggesting that the virus might have re-emerged after a long period of latency within a previously infected individual.
Published: 2021
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9. Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network

Author: Matthew T. Aliota, Nikos Vasilakis, Edward McSweegan, Leda Bassit, Michael J. Ricciardi, Thomas C. Friedrich, Guilherme S. Ribeiro, Natalia Mercer, Geraldine Schott-Lerner, George R. Saade, Thaddeus G. Golos, Shelton S. Bradrick, Diane E. Griffin, Mariano A. Garcia-Blanco, Lisa F. P. Ng, Pei Yong Shi, Diogo M. Magnani, Bryan Cox, Christina Gavegnano, Marc Lecuit, Chao Shan, Caroline Marrs, Andrew D. Haddow, David I. Watkins, Jorge E. Osorio, Scott C. Weaver, Raymond F. Schinazi, David H. O’Connor, Esper G. Kallas, Shannan L. Rossi, Uriel Kitron, University of Wisconsin-Madison, Emory University [Atlanta, GA], The University of Texas Medical Branch (UTMB), Global Virus Network, University of South Florida [Tampa] (USF), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Universidade de São Paulo = University of São Paulo (USP), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Miami Leonard M. Miller School of Medicine (UMMSM), Agency for science, technology and research [Singapore] (A*STAR), Universidade Federal da Bahia (UFBA), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Work from the authors’ laboratories was funded by in part by U.S. National Institutes of Health grants: R01NS087539-S1 (to DEG), R21AI129607 (to RFS), and R24AI120942, R01AI121452 (to SCW) R01 AI107157-01A1 (to TGG), R01AI116382-01A1S1 (to DHO), U01AI115577 (to NV) and P51 OD011106 (to the WNPRC)., U.S. Army Medical Research Institute of Infectious Diseases, University of São Paulo (USP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Génétiques Imagine [Paris], Fundação Oswaldo Cruz (FIOCRUZ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: 0301 basic medicine, Gerontology, medicine.medical_specialty, Asia, Sexual transmission, MALFORMAÇÕES, [SDV]Life Sciences [q-bio], Disease, Antiviral therapy, Nervous System Malformations, Arbovirus, Article, Zika virus, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Drug Discovery, Pandemic, Disease Transmission, Infectious, medicine, Animals, Maternal-fetal transmission, Pharmacology, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Diagnostic Tests, Routine, Zika Virus Infection, business.industry, Transmission (medicine), Public health, Outbreak, medicine.disease, biology.organism_classification, Infectious Disease Transmission, Vertical, 3. Good health, Congenital manifestations, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, Family medicine, Africa, Communicable Disease Control, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Americas, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In response to the outbreak of Zika virus (ZIKV) infection in the Western Hemisphere and the recognition of a causal association with fetal malformations, the Global Virus Network (GVN) assembled an international taskforce of virologists to promote basic research, recommend public health measures and encourage the rapid development of vaccines, antiviral therapies and new diagnostic tests. In this article, taskforce members and other experts review what has been learned about ZIKV-induced disease in humans, its modes of transmission and the cause and nature of associated congenital manifestations. After describing the make-up of the taskforce, we summarize the emergence of ZIKV in the Americas, Africa and Asia, its spread by mosquitoes, and current control measures. We then review the spectrum of primary ZIKV-induced disease in adults and children, sites of persistent infection and sexual transmission, then examine what has been learned about maternal-fetal transmission and the congenital Zika syndrome, including knowledge obtained from studies in laboratory animals. Subsequent sections focus on vaccine development, antiviral therapeutics and new diagnostic tests. After reviewing current understanding of the mechanisms of emergence of Zika virus, we consider the likely future of the pandemic.
Published: 2017
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10. GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 5: Entomological aspects

Author: Thomas Jaenisch, Anubis Vega-Rúa, Patrícia Brasil, M. G. Rosa-Freitas, Michael A. Drebot, P. Gallian, Sébastien Boyer, Maria Rios, Amadou A. Sall, Laura Pezzi, Anna-Bella Failloux, Angelle Desiree LaBeaud, Lisa F. P. Ng, Michael S. Diamond, Ricardo Lourenço-de-Oliveira, Guilherme S. Ribeiro, Scott C. Weaver, Mariama Dalanda Diallo, Nikos Vasilakis, A. J. Rodriguez-Morales, Alain Kohl, François Simon, Michael P. Busch, André Siqueira, Chantal Reusken, Jan Felix Drexler, Johan Neyts, Graham Simmons, X. de Lamballerie, Marc Lecuit, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), EA Bioscope Corse Méditerranée : Dynamique des infections virales en milieu insulaire, Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Fundação Oswaldo Cruz (FIOCRUZ), Institut Pasteur de la Guadeloupe, Agency for science, technology and research [Singapore] (A*STAR), Institut Pasteur du Cambodge, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Centre for Infection Research (DZIF), The University of Texas Medical Branch (UTMB), MRC - University of Glasgow Centre for Virus Research, Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), University of California [San Francisco] (UC San Francisco), University of California (UC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Public Health Agency of Canada, Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Heidelberg University Hospital [Heidelberg], Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Rega Institute for Medical Research [Leuven, België], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidade Federal da Bahia (UFBA), Instituto Gonçalo Moniz / Gonçalo Moniz Research Centre - Fiocruz Bahia [Salvador, Brésil] (IGM), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), U.S. Food and Drug Administration (FDA), Universidad Tecnológica de Pereira [Colombie] (UTP), Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées, BUISINE, Soline, Virology, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP), Institut Pasteur [Paris], University of California [San Francisco] (UCSF), University of California, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Primates, Research Report, GloPID-R chikungunya, o'nyong-nyong and Mayaro virus Working Group, Aedes albopictus, [SDV]Life Sciences [q-bio], 030106 microbiology, Aedes aegypti, Mosquito Vectors, medicine.disease_cause, 03 medical and health sciences, Aedes, Virology, Anopheles, medicine, Animals, Humans, O'nyong-nyong Virus, Chikungunya, Haemagogus, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, Alphavirus Infections, Yellow fever, Outbreak, virus diseases, Central America, biology.organism_classification, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious disease (medical specialty), Africa, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Enzootic, Chikungunya Fever, Chikungunya virus
Abstract: The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through an enzootic cycle that has not been characterized yet, with Anopheles species as main vectors and humans as amplification hosts during epidemics. MAYV is transmitted by Haemagogus species in an enzootic cycle using non-human primates as the main amplification and maintenance hosts, and humans becoming sporadically infected when venturing in or nearby forest habitats. Here, we focused on the transmission cycle and natural vectors that sustain circulation of these viruses in their respective locations. The knowledge of the natural ecology of transmission and the capacity of different vectors to transmit these viruses is crucial to understand CHIKV emergence, and to assess the risk that MAYV and ONNV will expand on wide scale using anthropophilic mosquito species not normally considered primary vectors. Finally, the experts identified knowledge gaps and provided adapted recommendations, in order to address future entomological investigations in the right direction. ispartof: ANTIVIRAL RESEARCH vol:174 ispartof: location:Netherlands status: published
Published: 2019
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11. GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 2: Epidemiological distribution of o'nyong-nyong virus

Author: M. G. Rosa-Freitas, Sébastien Boyer, A. J. Rodriguez-Morales, Jan Felix Drexler, Thomas Jaenisch, Patrícia Brasil, Johan Neyts, François Simon, Anna-Bella Failloux, de Lamballerie X, Lisa F. P. Ng, Michael A. Drebot, Pierre Gallian, Guilherme S. Ribeiro, Maria Rios, Amadou A. Sall, Chantal Reusken, Marc Lecuit, Scott C. Weaver, Michael P. Busch, Nikos Vasilakis, André Siqueira, A. Vega Rua, Angelle Desiree LaBeaud, Mawlouth Diallo, Michael S. Diamond, Alain Kohl, Ricardo Lourenço-de-Oliveira, Laura Pezzi, Graham Simmons, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [UNIV Corse-Inserm] (EA7310), Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), The University of Texas Medical Branch (UTMB), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées, Heidelberg University Hospital [Heidelberg], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), Institut Pasteur du Cambodge, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), University of California [San Francisco] (UC San Francisco), University of California (UC), Washington University in Saint Louis (WUSTL), Public Health Agency of Canada, MRC - University of Glasgow Centre for Virus Research, Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Agency for science, technology and research [Singapore] (A*STAR), Universidade Federal da Bahia (UFBA), U.S. Food and Drug Administration (FDA), Universidad Tecnológica de Pereira [Colombie] (UTP), Institut Pasteur de la Guadeloupe, Publication fees were covered by the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP), Humboldt-Universität zu Berlin, Institut Pasteur [Paris], Fundação Oswaldo Cruz (FIOCRUZ), University of California [San Francisco] (UCSF), University of California, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Virology, and DEMESLAY GOUGAM, MARIE
Subjects: 0301 basic medicine, GloPID-R chikungunya, o'nyong-nyong and Mayaro virus Working Group, Genes, Viral, Iron, 030106 microbiology, Prevalence, Alphavirus, medicine.disease_cause, Disease Outbreaks, 03 medical and health sciences, Seroepidemiologic Studies, Virology, Environmental health, medicine, Seroprevalence, Animals, Humans, O'nyong-nyong Virus, Serologic Tests, Chikungunya, Phylogeny, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pharmacology, Molecular epidemiology, Alphavirus Infections, Outbreak, 3. Good health, 030104 developmental biology, Geography, Infectious disease (medical specialty), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Africa, Chikungunya Fever, Chikungunya virus
Abstract: The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to identify gaps of knowledge about the natural history, epidemiology and medical management of infection by these viruses, and to provide adapted recommendations for future investigations. Here, we present a report dedicated to ONNV epidemiological distribution. Two large-scale ONNV outbreaks have been identified in Africa in the last 60 years, interspersed with sporadic serosurveys and case reports of returning travelers. The assessment of the real scale of ONNV circulation in Africa remains a difficult task and surveillance studies are necessary to fill this gap. The identification of ONNV etiology is made complicated by the absence of multiplex tools in co-circulation areas and that of reference standards, as well as the high cross-reactivity with related pathogens observed in serological tests, in particular with CHIKV. This is a specific obstacle for seroprevalence studies, that necessitate an improvement of serological tools to provide robust results. The scarcity of existent genetic data currently limits molecular epidemiology studies. ONNV epidemiology would also benefit from reinforced entomological and environmental surveillance. Finally, the natural history of the disease deserves to be further investigated, with a specific attention paid to long-term complications. Considering our incomplete knowledge on ONNV distribution, GloPID-R CHIKV, ONNV and MAYV experts recommend that a major effort should be done to fill existing gaps. ispartof: ANTIVIRAL RESEARCH vol:172 ispartof: location:Netherlands status: published
Published: 2019
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12. GloPID-R report on Chikungunya, O'nyong-nyong and Mayaro virus, part I: Biological diagnostics

Author: A. J. Rodriguez-Morales, M. G. Rosa-Freitas, Guilherme S. Ribeiro, Nikos Vasilakis, Lisa F. P. Ng, Mariama Dalanda Diallo, Scott C. Weaver, Patrícia Brasil, Jan Felix Drexler, Johan Neyts, Anna-Bella Failloux, François Simon, Alain Kohl, A. Vega Rua, Maria Rios, Michael P. Busch, Michael S. Diamond, André Siqueira, Michael A. Drebot, P. Gallian, Sébastien Boyer, Ricardo Lourenço-de-Oliveira, Chantal Reusken, Angelle Desiree LaBeaud, Thomas Jaenisch, Marc Lecuit, Laura Pezzi, X. de Lamballerie, Graham Simmons, Amadou A. Sall, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [UNIV Corse-Inserm] (EA7310), Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), The University of Texas Medical Branch (UTMB), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), German Centre for Infection Research (DZIF), University of California [San Francisco] (UC San Francisco), University of California (UC), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Washington University in Saint Louis (WUSTL), Public Health Agency of Canada, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Universidade Federal da Bahia (UFBA), University of Glasgow, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Agency for science, technology and research [Singapore] (A*STAR), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Institut Pasteur du Cambodge, Institut Pasteur de Dakar, Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), Heidelberg University Hospital [Heidelberg], Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), U.S. Food and Drug Administration (FDA), Universidad Tecnológica de Pereira [Colombie] (UTP), Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées, Institut Pasteur de la Guadeloupe, Publication fees were covered by the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP), Humboldt-Universität zu Berlin, University of California [San Francisco] (UCSF), University of California, Fundação Oswaldo Cruz (FIOCRUZ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Virology, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Humboldt Universität zu Berlin, Stanford University School of Medicine [Stanford], Stanford University [Stanford], Washington University in St Louis, Federal University of Bahia, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Arbovirus et Insectes Vecteurs, and Rega Institute for Medical Research
Subjects: 0301 basic medicine, medicine.medical_specialty, Genes, Viral, 030106 microbiology, Disease, Alphavirus, Mosquito Vectors, Cross Reactions, medicine.disease_cause, Antibodies, Viral, Communicable Diseases, Emerging, Virus, 03 medical and health sciences, Seroepidemiologic Studies, Virology, O'nyong-nyong, Epidemiology, medicine, Animals, Humans, O'nyong-nyong Virus, Chikungunya, Pathology, Molecular, Diagnostics, Phylogeny, Pharmacology, biology, business.industry, Alphavirus Infections, Outbreak, biology.organism_classification, Mayaro virus, 3. Good health, 030104 developmental biology, Cryoglobulinemia, Infectious disease (medical specialty), Preparedness, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, business, Chikungunya virus
Abstract: The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) Chikungunya (CHIKV), O'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group is investigating the natural history, epidemiology and medical management of infection by these viruses, to identify knowledge gaps and to propose recommendations for direct future investigations and rectification measures. Here, we present the first report dedicated to diagnostic aspects of CHIKV, ONNV and MAYV. Regarding diagnosis of the disease at the acute phase, molecular assays previously described for the three viruses require further evaluation, standardized protocols and the availability of international standards representing the genetic diversity of the viruses. Detection of specific IgM would benefit from further investigations to clarify the extent of cross-reactivity among the three viruses, the sensitivity of the assays, and the possible interfering role of cryoglobulinaemia. Implementation of reference panels and external quality assessments for both molecular and serological assays is necessary. Regarding sero-epidemiological studies, there is no reported high-throughput assay that can distinguish among these different viruses in areas of potential co-circulation. New specific tools and/or improved standardized protocols are needed to enable large-scale epidemiological studies of public health relevance to be performed. Considering the high risk of future CHIKV, MAYV and ONNV outbreaks, the Working Group recommends that a major investigation should be initiated to fill the existing diagnostic gaps. ispartof: ANTIVIRAL RESEARCH vol:166 pages:66-81 ispartof: location:Netherlands status: published
Published: 2019
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13. NLRP3 inflammasome activation drives tau pathology

Author: Shuangshuang Zhang, David Blum, Ana Vieira-Saecker, Carmen Venegas, Rakez Kayed, Hannah Scheiblich, Douglas T. Golenbock, Maximilian Merten, Shadi Albasset, Susanne V. Schmidt, Eicke Latz, Luc Buée, Frederic Brosseron, Sabine Opitz, Angelika Griep, Francesco Santarelli, Christina Ising, James Stunden, Róisín M. McManus, Michael T. Heneka, Dario Tejera, Stephanie Schwartz, Blum, David, Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Institute of Innate Immunity, Bonn, Department of Neurology, The University of Texas Medical Branch (UTMB), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Inflammasomes, metabolism [NLR Family, Pyrin Domain-Containing 3 Protein], physiopathology [Protein Aggregation, Pathological], Protein aggregation, genetics [Gene Expression Regulation], Mice, 0302 clinical medicine, genetics [Inflammasomes], Phosphorylation, Multidisciplinary, Microglia, integumentary system, Chemistry, Kinase, Caspase 1, Neurodegeneration, pathology [Microglia], Inflammasome, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:500, medicine.drug, tau Proteins, Protein Aggregation, Pathological, Article, 03 medical and health sciences, Alzheimer Disease, mental disorders, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroinflammation, genetics [NLR Family, Pyrin Domain-Containing 3 Protein], Amyloid beta-Peptides, Cyclin-dependent kinase 5, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Cyclin-Dependent Kinase 5, medicine.disease, metabolism [tau Proteins], Mice, Inbred C57BL, genetics [tau Proteins], 030104 developmental biology, Gene Expression Regulation, metabolism [Cyclin-Dependent Kinase 5], Neuroscience, metabolism [Inflammasomes], 030217 neurology & neurosurgery
Abstract: International audience; Alzheimer's disease is characterized by the accumulation of amyloid-beta in plaques, aggregation of hyperphosphorylated tau in neurofibrillary tangles and neuroinflammation, together resulting in neurodegeneration and cognitive decline1. The NLRP3 inflammasome assembles inside of microglia on activation, leading to increased cleavage and activity of caspase-1 and downstream interleukin-1β release2. Although the NLRP3 inflammasome has been shown to be essential for the development and progression of amyloid-beta pathology in mice3, the precise effect on tau pathology remains unknown. Here we show that loss of NLRP3 inflammasome function reduced tau hyperphosphorylation and aggregation by regulating tau kinases and phosphatases. Tau activated the NLRP3 inflammasome and intracerebral injection of fibrillar amyloid-beta-containing brain homogenates induced tau pathology in an NLRP3-dependent manner. These data identify an important role of microglia and NLRP3 inflammasome activation in the pathogenesis of tauopathies and support the amyloid-cascade hypothesis in Alzheimer's disease, demonstrating that neurofibrillary tangles develop downstream of amyloid-beta-induced microglial activation.
Published: 2019
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14. Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome

Author: Haiying Chen, Jerónimo Pachón, Judith Berastegui-Cabrera, Javier Sánchez-Céspedes, Marta Carretero-Ledesma, Eric A. Wold, Jimin Xu, Jia Zhou, Yu Xue, Universidad de Sevilla. Departamento de Medicina, [Xu,J, Chen,H, Xue,Y, Wold,EA, Zhou,J] Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX, USA. [Berastegui-Cabrera,J, Carretero-Ledesma,M, Pachón,J, Sánchez-Céspedes,J] Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío, CSIC, University of Seville, Seville, Spain. [Pachón,J] Department of Medicine, University of Seville, Seville, Spain., and This work was partially supported by the UTMB Technology Commercialization Program, the John D. Stobo, M. D. Distinguished Chair Endowment Fund (to JZ) and John Sealy Memorial Endowment Fund at UTMB, Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by the European Development Regional Fund 'A way to achieve Europe', Operative program Intelligent Growth 20142020, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI15/00489) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program 'Nicolás Monardes' (C-0059-2018) Servicio Andaluz de Salud, Junta de Andalucía. E.A.W. is supported by the National Institutes of Health (NIH) National Research Service Award (NRSA) F31 DA04551.
Subjects: entry inhibition, 0301 basic medicine, Salicylamide, Virus Replication, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], lcsh:Chemistry, Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Small Molecule Libraries [Medical Subject Headings], Drug Discovery, Salicylamides, Antivíricos, lcsh:QH301-705.5, Spectroscopy, Niclosamide, Infecciones, Chemistry, virus diseases, adenovirus, General Medicine, Chemicals and Drugs::Organic Chemicals::Amides::Anilides::Salicylanilides::Niclosamide [Medical Subject Headings], Small molecule, Virus, Computer Science Applications, Organisms::Viruses::DNA Viruses::Adenoviridae::Mastadenovirus::Adenoviruses, Human [Medical Subject Headings], Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Transformed::HEK293 Cells [Medical Subject Headings], Lytic cycle, Phenomena and Processes::Microbiological Phenomena::Virus Physiological Phenomena::Virus Physiological Processes::Virus Internalization [Medical Subject Headings], salicylamide derivatives, Niclosamida, medicine.drug, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery [Medical Subject Headings], medicine.drug_class, Endosome, Chemicals and Drugs::Organic Chemicals::Amides::Salicylamides [Medical Subject Headings], 030106 microbiology, Endosomes, Antiviral Agents, Endosomas, Article, Catalysis, Adenoviridae, Small Molecule Libraries, antiviral agent, Inorganic Chemistry, Inhibitory Concentration 50, 03 medical and health sciences, Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Endosomes [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50 [Medical Subject Headings], medicine, Humans, Physical and Theoretical Chemistry, Molecular Biology, Adenoviruses, Human, Organic Chemistry, Virus Internalization, Virology, eye diseases, Phenomena and Processes::Microbiological Phenomena::Microbiological Processes::Virus Physiological Processes::Viral Tropism [Medical Subject Headings], Viral Tropism, Phenomena and Processes::Microbiological Phenomena::Microbiological Processes::Virus Physiological Processes::Virus Replication [Medical Subject Headings], HEK293 Cells, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, A549 Cells, Tissue tropism, Antiviral drug
Abstract: Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI &gt, 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.
Published: 2021
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15. Meeting the challenge of tick-borne disease control: A proposal for 1000 Ixodes genomes

Author: Timothy J. Kurtti, Karen D. McCoy, Ala E. Tabor, Lesley Bell-Sakyi, Claude Rispe, Manuel Rodriguez Valle, Ulrike G. Munderloh, Benjamin L. Makepeace, Catherine A. Hill, Jyothi Thimmapuram, José de la Fuente, Maria V. Murgia, Saravanan Thangamani, Olivier Plantard, Ben J. Mans, Purdue University [West Lafayette], University of Liverpool, Instituto de Investigación en Recursos Cinegéticos (IREC), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, University of South Africa (UNISA), Evolution of host-microbe communities (MIVEGEC-EVCO), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), University of Queensland [Brisbane], The University of Texas Medical Branch (UTMB), University of Minnesota [Twin Cities], Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Institut National de la Recherche Agronomique (INRA)
Subjects: Ixodes ricinus, [SDV]Life Sciences [q-bio], education, 030231 tropical medicine, Tick, Microbiology, Genome, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Tick-borne disease, biology, Ixodes, Genomics, biology.organism_classification, medicine.disease, Infectious Diseases, Evolutionary biology, Tick-Borne Diseases, Insect Science, Parasitology
Abstract: International audience
Published: 2019
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16. Changes in the Transmission Dynamic of Chikungunya Virus in Southeastern Senegal

Author: Scott C. Weaver, Oumar Ndiaye, Abdourahmane Sow, Mawlouth Diallo, Bakary Djilocalisse Sadio, Amadou A. Sall, Ousmane Faye, Anta Tall Dia, Birgit Nikolay, Oumar Faye, Denis Malvy, Jorge Cano, Simon Cauchemez, Arbovirus et Virus de Fièvres Hémorragiques [Dakar, Sénégal], Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modélisation mathématique des maladies infectieuses, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), London School of Hygiene and Tropical Medicine (LSHTM), Unité d'Entomologie Médicale [Dakar] (UEM), The University of Texas Medical Branch (UTMB), The research was supported by the National Institutes of Health (NIH), Grant Number AI1069145., Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Limouzin, Cécile
Subjects: Male, Rural Population, 0301 basic medicine, Veterinary medicine, lcsh:QR1-502, environmental risk, MESH: Chikungunya Fever, Forests, Antibodies, Viral, medicine.disease_cause, Logistic regression, spatial autocorrelation, Population density, lcsh:Microbiology, law.invention, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Rural Population, Seroepidemiologic Studies, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], law, MESH: Child, Chikungunya, Child, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], Aged, 80 and over, MESH: Aged, MESH: Immunoglobulin G, MESH: Middle Aged, Age Factors, virus diseases, Middle Aged, MESH: Forests, MESH: Mining, MESH: Infant, Senegal, 3. Good health, Infectious Diseases, Transmission (mechanics), MESH: Young Adult, Child, Preschool, Female, Sylvatic cycle, Adult, Adolescent, MESH: Population Density, 030231 tropical medicine, Environment, Biology, Article, Mining, gold mining, Young Adult, 03 medical and health sciences, MESH: Senegal, Virology, medicine, Humans, Seroprevalence, MESH: Environment, Aged, Population Density, MESH: Adolescent, MESH: Age Factors, MESH: Seroepidemiologic Studies, MESH: Humans, MESH: Child, Preschool, Infant, Outbreak, MESH: Adult, Odds ratio, 15. Life on land, MESH: Male, 030104 developmental biology, Immunoglobulin G, Chikungunya Fever, MESH: Female, MESH: Antibodies, Viral
Abstract: In Senegal, chikungunya virus (CHIKV) is maintained in a sylvatic cycle and causes sporadic cases or small outbreaks in rural areas. However, little is known about the influence of the environment on its transmission. To address the question, 120 villages were randomly selected in the Kedougou region of southeastern Senegal. In each selected village, 10 persons by randomly selected household were sampled and tested for specific anti-CHIKV IgG antibodies by ELISA. We investigated the association of CHIKV seroprevalence with environmental variables using logistic regression analysis and the spatial correlation of village seroprevalence based on semivariogram analysis. Fifty-four percent (51%&ndash, 57%) of individuals sampled during the survey tested positive for CHIKV-specific IgG. CHIKV seroprevalence was significantly higher in populations living close to forested areas (Normalized Difference Vegetation Index (NDVI), Odds Ratio (OR) = 1.90 (1.42&ndash, 2.57)), and was negatively associated with population density (OR = 0.76 (0.69&ndash, 0.84)). In contrast, in gold mining sites where population density was &gt, 400 people per km2, seroprevalence peaked significantly among adults (46% (27%&ndash, 67%)) compared to all other individuals (20% (12%&ndash, 31%)). However, traditional gold mining activities significantly modify the transmission dynamic of CHIKV, leading to a potential increase of the risk of human exposition in the region.
Published: 2020
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17. rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences

Author: Frédéric H.-T. Allain, Nicolas Charlet-Berguerand, Frank Ruffenach, John W. Day, Giovanni Meola, Masanori P. Takahashi, Chantal Sellier, Estefanía Cerro-Herreros, Jack Puymirat, Denis Furling, Angeline Gaucherot, Guillaume Bassez, Ruben Artero, Markus Blatter, Beatriz Llamusi, Fernande Freyermuth, Harutoshi Fujimura, Partha S. Sarkar, Bjarne Udd, Benedikt Schoser, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomedical Research Institute [Valencia, Spain] (INCLIVA ), Universitat de València (UV), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), The University of Texas Medical Branch (UTMB), Université Laval [Québec] (ULaval), Neurology Department, Tampere University Hospital, University of Helsinki, Stanford University, University of Milan, Università degli Studi di Milano, IRCCS Policlinico San Donato, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Toneyama National Hospital, Osaka University Graduate School of Medicine, Suita, Ludwig Maximilian University [Munich] (LMU), Medicum, Department of Medical and Clinical Genetics, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli Studi di Milano = University of Milan (UNIMI), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Models, Molecular, Protein Conformation, alpha-Helical, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Gene Expression, RNA-binding protein, Crystallography, X-Ray, chemistry.chemical_compound, MOLECULAR-BASIS, Gene expression, MBNL1, Myotonic Dystrophy, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, CHLORIDE CHANNEL, RNA-Binding Proteins, Recombinant Proteins, 3. Good health, Cell biology, CONGENITAL HEART-DISEASE, Drosophila melanogaster, Thermodynamics, SKELETAL-MUSCLE, RNA Splicing Factors, CUG REPEATS, Protein Binding, musculoskeletal diseases, STEADY-STATE, congenital, hereditary, and neonatal diseases and abnormalities, Science, RBFOX1, Biology, Myotonic dystrophy, Binding, Competitive, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Escherichia coli, Animals, Humans, Protein Interaction Domains and Motifs, Binding site, Nucleotide Motifs, Muscle, Skeletal, SPLICING REGULATOR RBFOX2, MUSCLEBLIND PROTEINS, Binding Sites, PRE-MESSENGER-RNA, RNA, General Chemistry, medicine.disease, Disease Models, Animal, Kinetics, 030104 developmental biology, chemistry, TRIPLET REPEAT, Protein Conformation, beta-Strand, 3111 Biomedicine
Abstract: Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle cells. Furthermore, expression of rbFOX1 corrects alternative splicing alterations and rescues muscle atrophy, climbing and flying defects caused by expression of expanded CCUG repeats in a Drosophila model of DM2., Myotonic dystrophy (DM) type 2 is a neuromuscular pathology caused by large expansions of CCTG repeats. Here the authors find that rbFOX1 RNA binding protein binds to CCUG RNA repeats and competes with MBNL1 for the binding to CCUG repeats, releasing MBNL1 from sequestration in DM2 muscle cells.
Published: 2018
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18. Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa

Author: James Orsborne, Thomas Walker, Fara Nantenaina Raharimalala, Francis Wat’senga, Kamil Khanipov, Mojca Kristan, Yuriy Fofanov, Yaw A. Afrane, Grant L. Hughes, Emile Z Manzambi, Kalil Keita, Seth R. Irish, Gena G. Lawrence, Eliot Hurn, Denka Camara, Claire L. Jeffries, Janvier Bandibabone, Georgiy Golovko, Shivanand Hegde, Sébastien Boyer, Tarekegn A. Abeku, Yaya Barry, Kirstin Spence, Luciano Michaël Tantely, Abdul Rahim Mohammed, Maria Pimenova, London School of Hygiene and Tropical Medicine (LSHTM), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, The University of Texas Medical Branch (UTMB), Centre de Recherche en Sciences Naturelles [Lwiro, Congo] (CRSN), Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Ministère de la Santé [Conakry, Guinea], Institut National de Recherche Biomédicale [Kinshasa] (INRB), University of Ghana, Malaria Consortium, London, UK, and CLJ and TW were supported by a Wellcome Trust /Royal Society grant awarded to TW (101285): http://www.wellcome.ac.uk
Subjects: 0301 basic medicine, Range (biology), media_common.quotation_subject, Anopheles gambiae, 030231 tropical medicine, malaria, Prevalence, Zoology, Medicine (miscellaneous), Asaia, Insect, Plasmodium, General Biochemistry, Genetics and Molecular Biology, symbols.namesake, 03 medical and health sciences, endosymbionts, 0302 clinical medicine, Anopheles, parasitic diseases, medicine, Parasite hosting, Microbiome, reproductive and urinary physiology, mosquitoes, 030304 developmental biology, media_common, Sanger sequencing, 0303 health sciences, biology, fungi, Articles, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, symbols, Multilocus sequence typing, bacteria, Wolbachia, Malaria, Research Article
Abstract: Background: Wolbachia, a common insect endosymbiotic bacterium that can influence pathogen transmission and manipulate host reproduction, has historically been considered absent from the Anopheles (An.) genera, but has recently been found in An. gambiae s.l. populations in West Africa. As there are numerous Anopheles species that have the capacity to transmit malaria, we analysed a range of species across five malaria endemic countries to determine Wolbachia prevalence rates, characterise novel Wolbachia strains and determine any correlation between the presence of Plasmodium, Wolbachia and the competing bacterium Asaia. Methods: Anopheles adult mosquitoes were collected from five malaria-endemic countries: Guinea, Democratic Republic of the Congo (DRC), Ghana, Uganda and Madagascar, between 2013 and 2017. Molecular analysis was undertaken using quantitative PCR, Sanger sequencing, Wolbachia multilocus sequence typing (MLST) and high-throughput amplicon sequencing of the bacterial 16S rRNA gene. Results: Novel Wolbachia strains were discovered in five species: An. coluzzii, An. gambiae s.s., An. arabiensis, An. moucheti and An. species A, increasing the number of Anopheles species known to be naturally infected. Variable prevalence rates in different locations were observed and novel strains were phylogenetically diverse, clustering with Wolbachia supergroup B strains. We also provide evidence for resident strain variants within An. species A. Wolbachia is the dominant member of the microbiome in An. moucheti and An. species A but present at lower densities in An. coluzzii. Interestingly, no evidence of Wolbachia/Asaia co-infections was seen and Asaia infection densities were shown to be variable and location dependent. Conclusions: The important discovery of novel Wolbachia strains in Anopheles provides greater insight into the prevalence of resident Wolbachia strains in diverse malaria vectors. Novel Wolbachia strains (particularly high-density strains) are ideal candidate strains for transinfection to create stable infections in other Anopheles mosquito species, which could be used for population replacement or suppression control strategies.
Published: 2018
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19. Biochemistry and Molecular Biology of Flaviviruses

Author: Mariano A. Garcia-Blanco, K. Reddisiva Prasanth, Nicholas J. Barrows, Kuo-Chieh Liao, Ruben Soto-Acosta, Rafael K. Campos, October M. Sessions, Geraldine Schott-Lerner, Julien Pompon, Shelton S. Bradrick, Shih Chia Yeh, University of Texas Medical Branch at Galveston, Duke University [Durham], Duke-NUS Medical School [Singapore], The University of Texas Medical Branch (UTMB), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])
Subjects: 0301 basic medicine, Genes, Viral, viruses, RNA-binding protein, Virus Replication, Genome, Virus, Article, Dengue fever, 03 medical and health sciences, medicine, Humans, Gene, Chemistry, Flavivirus, RNA-Binding Proteins, General Chemistry, Japanese encephalitis, biochemical phenomena, metabolism, and nutrition, medicine.disease, Non-coding RNA, Molecular biology, 3. Good health, 030104 developmental biology, Viral replication, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Host-Pathogen Interactions
Abstract: International audience; Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.
Published: 2018
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20. Assessing the epidemiological effect of wolbachia for dengue control

Author: Scott Leslie O'Neill, Neil M. Ferguson, Thomas W. Scott, Louis Lambrechts, Peter A. Ryan, Scott C. Weaver, Cameron P. Simmons, Elizabeth A. McGraw, Scott A. Ritchie, Eva Harris, Eng Eong Ooi, Edward C. Holmes, Interactions Virus-Insectes (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], MRC Centre for Outbreak Analysis and Modelling [London], Imperial College London, Division of Infectious Diseases and Vaccinology, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, School of Biological Sciences [Clayton], Monash University [Clayton], Duke-National University of Singapore Graduate Medical School, School of Public Health and Tropical Medicine and Rehabilitative Sciences, James Cook University (JCU), Fogarty International Center, National Institutes of Health [Bethesda] (NIH), Department of Entomology and Nematology, University of California [Davis] (UC Davis), University of California-University of California, Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Centre for Tropical Medicine, Nossal Institute of Global Health, University of Melbourne, Institute for Human Infections and Immunity and Department of Pathology, The University of Texas Medical Branch (UTMB), This work was supported by a grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill & Melinda Gates Foundation, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of California (UC)-University of California (UC), and University of Oxford
Subjects: and promotion of well-being, Dengue virus, medicine.disease_cause, Dengue fever, Dengue, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Aedes, Seroepidemiologic Studies, Epidemiology, 2.2 Factors relating to the physical environment, Aetiology, Randomized Controlled Trials as Topic, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, 3. Good health, Human morbidity, Mosquito control, Infectious Diseases, Research Design, Medical Microbiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Public Health and Health Services, Wolbachia, Infection, medicine.medical_specialty, Clinical Sciences, Computational biology, Microbiology, Virus, Article, Rare Diseases, parasitic diseases, medicine, Animals, Humans, Pest Control, Biological, 3.2 Interventions to alter physical and biological environmental risks, Prevention, Dengue Virus, biology.organism_classification, medicine.disease, Biological, Prevention of disease and conditions, Virology, Insect Vectors, Vector-Borne Diseases, Emerging Infectious Diseases, Good Health and Well Being, Geographical cluster, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pest Control, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Dengue viruses cause more human morbidity and mortality than any other arthropod-borne virus. Dengue prevention relies mainly on vector control; however, the failure of traditional methods has promoted the development of novel entomological approaches. Although use of the intracellular bacterium wolbachia to control mosquito populations was proposed 50 years ago, only in the past decade has its use as a potential agent of dengue control gained substantial interest. Here, we review evidence that supports a practical approach for dengue reduction through field release of wolbachia-infected mosquitoes and discuss the additional studies that have to be done before the strategy can be validated and implemented. A crucial next step is to assess the efficacy of wolbachia in reducing dengue virus transmission. We argue that a cluster randomised trial is at this time premature because choice of wolbachia strain for release and deployment strategies are still being optimised. We therefore present a pragmatic approach to acquiring preliminary evidence of efficacy through various complementary methods including a prospective cohort study, a geographical cluster investigation, virus phylogenetic analysis, virus surveillance in mosquitoes, and vector competence assays. This multipronged approach could provide valuable intermediate evidence of efficacy to justify a future cluster randomised trial.
Published: 2015
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21. Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases

Author: Scott C. Weaver, Caroline Charlier, Nikos Vasilakis, Marc Lecuit, The University of Texas Medical Branch (UTMB), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Institut des Maladies Génétiques Imagine [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, chikungunya, viruses, 030231 tropical medicine, mosquito, Aedes aegypti, Mosquito Vectors, Biology, medicine.disease_cause, Arbovirus, Communicable Diseases, Emerging, General Biochemistry, Genetics and Molecular Biology, Article, Dengue fever, yellow fever, 03 medical and health sciences, 0302 clinical medicine, Zika, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Animals, Humans, Chikungunya, Rift Valley fever, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Zika Virus Infection, Yellow fever, virus diseases, General Medicine, Japanese encephalitis, medicine.disease, biology.organism_classification, Virology, dengue, 3. Good health, 030104 developmental biology, arbovirus, Virus Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Enzootic, Chikungunya Fever, Arboviruses, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Dengue, yellow fever, chikungunya, and Zika viruses have undergone such urban emergence. We focus mainly on the latter two, which are recent arrivals in the Western Hemisphere. We also discuss a few other viruses with the potential to emerge through all of these mechanisms.
Published: 2018
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22. Chikungunya Outbreak in Kedougou, Southeastern Senegal in 2009-2010

Author: Manfred Weidmann, Cheikh Tidiane Diagne, Abdourahmane Sow, Rubing Chen, Amadou A. Sall, Oumar Ndiaye, Mathilde Guerbois, Scott C. Weaver, Ousmane Faye, Diawo Diallo, Abdourahmane Faye, Cheikh Sadibou Senghor, Youssoupha Ndiaye, Mawlouth Diallo, Bakary Djilocalisse Sadio, Anta Tall Dia, Oumar Faye, Denis Malvy, Kathryn A. Hanley, Douglas M. Watts, Ousmane M. Diop, Arbovirus et Virus de Fièvres Hémorragiques [Dakar, Sénégal], Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau International des Instituts Pasteur (RIIP), The University of Texas Medical Branch (UTMB), University Medical Center Göttingen (UMG), District sanitaire de Saraya, District sanitaire de Kedougou, University of Texas [El Paso] (UTEP ), New Mexico State University, and The research was funded by the National Institutes of Health (Grant Number 5R01A 1069145).
Subjects: 0301 basic medicine, sylvatic circulation, 030231 tropical medicine, medicine.disease_cause, Chikungunya fever, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Major Article, Chikungunya, Viral isolation, Aedes, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, School age child, biology, outbreak, business.industry, Outbreak, virus diseases, biology.organism_classification, Senegal, 3. Good health, Kedougou, 030104 developmental biology, Infectious Diseases, Oncology, Ethnology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Chikungunya virus
Abstract: Background In Senegal, Chikungunya virus (CHIKV), which is an emerging mosquito-borne alphavirus, circulates in a sylvatic and urban/domestic cycle and has caused sporadic human cases and epidemics since 1960s. However, the real impact of the CHIKV sylvatic cycle in humans and mechanisms underlying its emergence still remains unknown. Methodology One thousand four hundred nine suspect cases of CHIKV infection, recruited from 5 health facilities located in Kedougou region, south-eastern Senegal, between May 2009 to March 2010, together with 866 serum samples collected from schoolchildren from 4 elementary schools in May and November 2009 from Kedougou were screened for anti-CHIKV immunoglobulin (Ig)M antibodies and, when appropriate, for viral nucleic acid by real-time polymerase chain reaction (rPCR) and virus isolation. In addition, mosquitoes collected in the same area from May 2009 to January 2010 were tested for CHIKV by rPCR and by virus isolation, and 116 monkeys sera collected from March 2010 to May 2010 were tested for anti-CHIKV IgM and neutralizing antibodies. Results The main clinical manifestations of the CHIKV suspect cases were headache, myalgia, and arthralgia. Evidence for CHIKV infection was observed in 1.4% (20 of 1409) of patients among suspect cases. No significant difference was observed among age or sex groups. In addition, 25 (2.9%) students had evidence of CHIKV infection in November 2009. Chikungunya virus was detected in 42 pools of mosquitoes, mainly from Aedes furcifer, and 83% of monkeys sampled were seropositive. Conclusions Our findings further documented that CHIKV is maintained in a sylvatic transmission cycle among monkeys and Aedes mosquitoes in Kedougou, and humans become infected by exposure to the virus in the forest.
Published: 2018
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23. Lactobacillus rhamnosus GG increases cyclooxygenase-2 expression and prostaglandin E2 secretion in colonic myofibroblasts via a MyD88-dependent mechanism during homeostasis

Author: Daniel L. Worthley, Maria C. Urdaci, Philippe Bressollier, Romain Villeger, Rachel Dillard, Don W. Powell, Gabriela Uribe, Irina V. Pinchuk, Timothy C. Wang, The University of Texas Medical Branch (UTMB), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Daniel Guggenheim School of Aerospace Engineering (GA TECH), Georgia Institute of Technology [Atlanta], Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), and Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Stromal cell, Colon, Immunology, Prostaglandin, Administration, Oral, Mice, Transgenic, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Microbiology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, Dinoprostone, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Downregulation and upregulation, Virology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, Homeostasis, Humans, Prostaglandin E2, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Myofibroblasts, ComputingMilieux_MISCELLANEOUS, Leukotriene, Innate immune system, Arachidonate 5-Lipoxygenase, Arachidonic Acid, Lacticaseibacillus rhamnosus, Probiotics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Mice, Inbred C57BL, 030104 developmental biology, Eicosanoid, chemistry, Cyclooxygenase 2, 030220 oncology & carcinogenesis, Myeloid Differentiation Factor 88, Cancer research, Caco-2 Cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, medicine.drug
Abstract: Prostaglandin E2 (PGE2 ) plays a critical role in intestinal mucosal tolerance and barrier integrity. Cyclooxygenase-2 (COX-2)-dependent PGE2 production involves mobilisation of arachidonic acid. Lactobacillus rhamnosus GG (LbGG) is one of the most widely used probiotics reported to colonise the colonic mucosa. LbGG contributes to the protection of the small intestine against radiation injury through the repositioning of mucosal COX-2 expressing cells. However, it is unknown if LbGG modulates PGE2 production in the colonic mucosa under homeostasis and the major cellular elements involved in these processes. Colonic epithelial and CD90+ mesenchymal stromal cells, also known as (myo) fibroblasts (CMFs), are abundant innate immune cells in normal colonic mucosa able to produce PGE2 . Herein, we tested the hypothesis that under colonic mucosal homeostasis, LbGG modulates the eicosanoid pathway resulting in increased PGE2 production in both epithelial and stromal cells. Among the five tested human colonic epithelial cell lines, only exposure of Caco-2 to LbGG for 24 hr led to the mobilisation of arachidonic acid with concomitant increase in the components within the leukotriene and COX-2-dependent PGE2 pathways. By contrast, CMFs isolated from the normal human colonic mucosa responded to LbGG with increased expression of COX-2 and PGE2 in the prostaglandin pathway, but not 5-LO in the leukotriene pathway. Oral gavage of C57BL/6 mice for 5 days with LbGG (5 × 108 Colony-Forming Unit (CFU)/dose) increased COX-2 expression in the colonic mucosa. The majority of cells upregulating COX-2 protein expression were located in the colonic lamina propria and colocalised with α-SMA+ cells corresponding to the CMF phenotype. This process was myeloid differentiation factor-88-dependent, because silencing of myeloid differentiation factor-88 expression in CMFs abrogated LbGG-induced upregulation of COX-2 in culture and in vivo. Taken together, our data suggest that LbGG increases release of COX-2-mediated PGE2 , contributing to the maintenance of mucosal homeostasis in the colon and CMFs are among the major contributors to this process.
Published: 2017
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24. Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined with FOLFOX Chemotherapy in Patients with Metastatic Colorectal Cancer

Author: Alain R. Thierry, Christine Megerdichian Parseghian, Ji Yuan Wu, Kanwal Pratap Singh Raghav, Feng Tian, Laura Henderson, Nila U. Parikh, Anastasia D. Katsiampoura, Marc Ychou, Scott Kopetz, Zhi-Qin Jiang, David G. Menter, Gary E. Gallick, Cathy Eng, David R. Fogelman, Robert A. Wolff, Michael J. Overman, Arvind Dasari, Brice Pastor, The University of Texas M.D. Anderson Cancer Center [Houston], The University of Texas Medical Branch (UTMB), Tsinghua University [Beijing] (THU), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), and CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Dasatinib, Leucovorin, Cetuximab, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, Disease-Free Survival, Article, CSK Tyrosine-Protein Kinase, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Aged, Chemotherapy, business.industry, Cancer, Middle Aged, medicine.disease, digestive system diseases, 3. Good health, ErbB Receptors, 030104 developmental biology, src-Family Kinases, 030220 oncology & carcinogenesis, Female, KRAS, Fluorouracil, business, Colorectal Neoplasms, MESH: Colorectal Neoplasms, medicine.drug, Proto-oncogene tyrosine-protein kinase Src
Abstract: Purpose: Aberrant activation of the intracellular tyrosine kinase Src has been implicated as a mechanism of acquired chemotherapy resistance in metastatic colorectal cancer (mCRC). Here, the oral tyrosine kinase Src inhibitor, dasatinib, was investigated in combination with FOLFOX and cetuximab. Experimental Design: We performed a phase IB/II study of 77 patients with previously treated mCRC. Primary objectives were to determine the maximum tolerated dose, dose-limiting toxicities (DLT), pharmacodynamics, and efficacy. Using a 3 + 3 design, patients received FOLFOX6 with cetuximab and escalating doses of dasatinib (100, 150, 200 mg daily), followed by a 12-patient expansion cohort at 150 mg. Phase II studies evaluated FOLFOX plus dasatinib 100 mg in KRAS c12/13mut patients or in combination with cetuximab if KRAS c12/13WT. FAK and paxillin were utilized as surrogate blood biomarkers of Src inhibition, and paired biopsies of liver metastases were obtained in patients in the expansion cohort. Results: In phase IB, the DLTs were grade 3/4 fatigue (20%) and neutropenia (23%). In phase II, grade 3/4 fatigue (23%) and pleural effusions (11%) were present. Response rates were 20% (6 of 30) in the phase IB escalation and expansion cohort and 13% (3 of 24) and 0% (0 of 23) in the KRAS c12/13WT and mutant cohorts of phase II, respectively. Median progression-free survival was 4.6, 2.3, and 2.3 months, respectively. There was no evidence of Src inhibition based on surrogate blood biomarkers or paired tumor biopsies. Conclusions: The combination of dasatinib plus FOLFOX with or without cetuximab showed only modest clinical activity in refractory colorectal cancer. This appears to be primarily due to a failure to fully inhibit Src at the achievable doses of dasatinib. The combination of dasatinib plus FOLFOX with or without cetuximab did not show meaningful clinical activity in refractory colorectal cancer due to failure to fully inhibit Src. Clin Cancer Res; 23(15); 4146–54. ©2017 AACR.
Published: 2017
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25. Chikungunya Virus–Vector Interactions

Author: Lark L. Coffey, Scott C. Weaver, Anna-Bella Failloux, University of California [Davis] (UC Davis), University of California (UC), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), The University of Texas Medical Branch (UTMB), University of California, and Institut Pasteur [Paris]
Subjects: chikungunya, lcsh:QR1-502, mosquito, Review, adaptation, MESH: Chikungunya Fever, MESH: Insect Vectors, Alphavirus, Disease, medicine.disease_cause, lcsh:Microbiology, Virus, Viral vector, Virology, medicine, Animals, Humans, MESH: Animals, Chikungunya, MESH: Humans, biology, Host (biology), MESH: Host-Pathogen Interactions, transmission, virus diseases, MESH: Chikungunya virus, biology.organism_classification, Insect Vectors, 3. Good health, Culicidae, Infectious Diseases, Vector (epidemiology), Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, Biological dispersal, MESH: Culicidae, Chikungunya virus, vector
Abstract: International audience; Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed.
Published: 2014
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26. The neuroimmune basis of fatigue

Author: Lucile Capuron, Cobi J. Heijnen, Robert Dantzer, Annemieke Kavelaars, Sophie Layé, The University of Texas Medical Branch (UTMB), Nutrition et Neurobiologie intégrée (NutriNeuro), and Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS)
Subjects: Innate immune system, High prevalence, Neuroimmunomodulation, Extramural, [SDV]Life Sciences [q-bio], General Neuroscience, Central nervous system, Article, Immune system, medicine.anatomical_structure, Neurotrophic factors, medicine, Animals, Humans, Psychology, Neuroscience, Insula, Fatigue
Abstract: International audience; The exact nature and pathophysiology of fatigue remain largely elusive despite its high prevalence in physically ill patients. Studies on the relationship between the immune system and the central nervous system provide a new perspective on the mechanisms of fatigue. Inflammatory mediators that are released by activated innate immune cells at the periphery and in the central nervous system alter the metabolism and activity of neurotransmitters, generate neurotoxic compounds, decrease neurotrophic factors, and profoundly disturb the neuronal environment. The resulting alterations in fronto-striatal networks together with the activation of insula by inflammatory interoceptive stimuli underlie the many dimensions of fatigue including reduced incentive motivation, decreased behavioral flexibility, uncertainty about usefulness of actions, and awareness of fatigue.
Published: 2014
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27. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements

Author: Marco Vignuzzi, Magnus Fontes, Bryan C. Mounce, Ofer Isakov, Rubing Chen, Gonzalo Moratorio, Antoine Enfissi, Hervé Blanc, Kenneth A. Stapleford, Séverine Matheus, Rasmus Henningsson, Daphna Weissglas-Volkov, Myrielle Dupont-Rouzeyrol, Dominique Rousset, Scott C. Weaver, Noam Shomron, Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), International Group for Data Analysis (IGDA), Institut Pasteur [Paris] (IP), The University of Texas Medical Branch (UTMB), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Sackler Faculty of Medicine, Tel Aviv University (TAU), Institut Pasteur de Nouvelle-Calédonie, This work was supported by a Institut Pasteur Programme Transversal de Recherche PTR 489 grant, the French Government ’s Investissementd’Avenir program, Laboratoire d ’Excellence' Integrative Biology of Emerging Infectious Diseases ' grant ANR-10-LABX-62-IBEID) and a ' Equipe FRM DEQ20150331759 ' grant from the French Fondation pour la Recherche Médicale (KAS, MV). RC and SCW were supported by National institutes of Health Contract HHSN272201000040I/HHSN27200004/D04, and by the Institute for Human Infections and Immunity at the University of Texas Medical Branch. DWV was supported by the Edmond J. Safra Center for Bioinformatics and the Center for Nanoscience and nanotechnology at Tel-Aviv University., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Tel Aviv University [Tel Aviv], Stapleford K.A., Moratorio Gonzalo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. Instituto Pasteur, Henningsson R., Chen R., Matheus S., Enfissi A., Weissglas-Volkov D., Isakov O., Blanc H., Mounce B.C, Dupont-Rouzeyrol M., Shomron N., Weaver S., Fontes M., Rousset D., Vignuzz M., Calvez, Elodie, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: Pathology and Laboratory Medicine, Infographics, Geographical locations, Disease Outbreaks, Togaviridae, MESH: Genetic Variation, Chikungunya, MESH: Phylogeny, Phylogeny, education.field_of_study, MESH: Genomics, virus diseases, Phylogenetic Analysis, Genomics, Virus, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Caribbean Region, Medical Microbiology, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Caribbean Region, lcsh:RC955-962, Alphaviruses, 030106 microbiology, Molecular Sequence Data, Alphavirus, Viral quasispecies, Microbiology, Evolution, Molecular, 03 medical and health sciences, Humans, education, Molecular Biology Techniques, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Microbial Pathogens, Molecular Biology, Caribbean, Molecular Biology Assays and Analysis Techniques, MESH: Humans, MESH: Molecular Sequence Data, Data Visualization, Public Health, Environmental and Occupational Health, Organisms, Outbreak, Chikungunya Infection, Genetic Variation, MESH: Chikungunya virus, lcsh:RA1-1270, Virology, 030104 developmental biology, People and places, Cloning, 0301 basic medicine, RNA viruses, MESH: Sequence Analysis, DNA, Viral Diseases, viruses, [SDV]Life Sciences [q-bio], MESH: Chikungunya Fever, medicine.disease_cause, Medicine and Health Sciences, MESH: Disease Outbreaks, MESH: Evolution, Molecular, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Virus, biology, lcsh:Public aspects of medicine, Infectious Diseases, Viral evolution, Viruses, MESH: Genome, Viral, Pathogens, Martinique, Sequence Analysis, Graphs, Research Article, Computer and Information Sciences, lcsh:Arctic medicine. Tropical medicine, Population, Genome, Viral, Research and Analysis Methods, Viral Evolution, Togaviruses, medicine, Sequencing Techniques, Evolutionary Biology, Biology and life sciences, Sequence Analysis, DNA, biology.organism_classification, Genética, Organismal Evolution, North America, Microbial Evolution, Chikungunya Fever, Sequence Alignment
Abstract: Background Chikungunya virus (CHIKV), an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak. Methodology/Principle Findings We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3’ untranslated region (UTR) structure, not previously found in nature, that led to increased replication in insect cells. Conclusions/Significance Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3’UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naïve population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV., Author Summary Chikungunya virus is a re-emerging and rapidly spreading arbovirus that has caused several outbreaks in the last decade with the most recent in the Caribbean islands and the Americas beginning in 2013 infecting over 1 million individuals. The ability to monitor such epidemics would be enhanced by characterizing the viral populations that circulate within infected individuals. To do this, we deep-sequenced viral populations from infected individuals and identified minority variants present at high frequencies, as well as the presence of a novel 3’ untranslated genome region (UTR) structure, a key determinant of chikungunya virus infectivity and evolution never before described in nature. Finally, we genetically engineered an infectious clone from this outbreak strain and established that the novel 3’UTR structure increases viral replication in mosquito cells. Taken together these studies highlight the vast diversity of viral populations in infected individuals, reveal potential novel determinants of chikungunya virus biology, and provide an indispensable tool for future studies involved in viral evolution and adaptation.
Published: 2016
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28. The Global Virus Network: Challenging chikungunya

Author: Matthew B. Frieman, Scott C. Weaver, Marc Lecuit, Edward McSweegan, Sharon Hrynkow, Thomas E. Morrison, Global Virus Network, The University of Texas Medical Branch (UTMB), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Maryland School of Medicine, University of Maryland System, University of Colorado [Denver], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], University of South Florida [Tampa] (USF), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Resource (biology), International Cooperation, education, Public policy, Global Virus Network, Global Health, medicine.disease_cause, Article, Disease Outbreaks, West africa, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Global health, Humans, Medicine, Chikungunya, health care economics and organizations, Pharmacology, Western hemisphere, Arbovirus, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Task force, Public relations, Emerging virus, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Vector-borne, Communicable Disease Control, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The recent spread of chikungunya virus to the Western Hemisphere, together with the ongoing Ebola epidemic in West Africa, have highlighted the importance of international collaboration in the detection and management of disease outbreaks. In response to this need, the Global Virus Network (GVN) was formed in 2011. The GVN is a coalition of leading medical virologists in 34 affiliated laboratories in 24 countries, who collaborate to share their resources and expertise. The GVN supports research, promotes training for young scientists, serves as a technical resource for governments, businesses and international organizations, facilitates international scientific cooperation, and advocates for funding and evidence-based public policies. In response to the spread of chikungunya, the GVN formed a task force to identify research gaps and opportunities, including models of infection and disease, candidate vaccines and antivirals, epidemiology and vector control measures. Its members also serve as authoritative sources of information for the public, press, and policy-makers. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World".
Published: 2015
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29. Chikungunya Virus Infections

Author: Fabrice, Simon, Emilie, Javelle, Philippe, Gasque, The University of Texas Medical Branch (UTMB), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: viruses, [SDV]Life Sciences [q-bio], education, MESH: Chikungunya Fever, MESH: Insect Vectors, Chikungunya fever, medicine.disease_cause, Virus, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Medicine, Animals, Humans, MESH: Animals, 030212 general & internal medicine, Chikungunya, 030304 developmental biology, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, business.industry, virus diseases, MESH: Chikungunya virus, General Medicine, Virology, 3. Good health, Insect Vectors, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Culicidae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, Animals, Chikungunya Fever, Chikungunya virus, CULICIDAE, Humans, Insect Vectors, business, MESH: Culicidae, Chikungunya virus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Comment on Chikungunya virus and the global spread of a mosquito-borne disease. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015]; International audience; To the Editor and Response
Published: 2015
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30. Chikungunya Virus and the Global Spread of a Mosquito-Borne Disease

Author: Marc Lecuit, Scott C. Weaver, The University of Texas Medical Branch (UTMB), Global Virus Network, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Service des Maladies infectieuses et tropicales [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], We thank Therese Couderc, the members of the Biology of Infection Unit, and the members of the Chikungunya Task Force at Institut Pasteur, and Rose Langsjoen for assistance with graphics., University of South Florida [Tampa] (USF), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: musculoskeletal diseases, myalgia, viruses, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Disease, Alphavirus, MESH: Chikungunya Fever, MESH: Insect Vectors, medicine.disease_cause, Virus, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, MESH: Animals, Chikungunya, MESH: Disease Outbreaks, MESH: Travel, 030304 developmental biology, Mosquito-borne disease, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, biology, business.industry, virus diseases, MESH: Chikungunya virus, General Medicine, medicine.disease, biology.organism_classification, Virology, Rash, 3. Good health, body regions, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Chikungunya Virus Infection, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Disease Progression, medicine.symptom, business, MESH: Culicidae, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Comment in Chikungunya Virus Infections. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015]; International audience; Chikungunya virus is a mosquito-borne alphavirus; its name comes from a Makonde word describing the bent posture of persons with the severe arthralgia that is a hallmark of chikungunya fever, the disease caused by the virus.1 Chikungunya virus was first isolated after a 1952–1953 epidemic in present-day Tanzania. Outbreaks were subsequently identified in Asia during the 1950s and 1960s [...]
Published: 2015
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31. ISG15 is critical in the control of Chikungunya virus infection independent of UbE1L mediated conjugation

Author: Clémentine Schilte, Stephen Higgs, Matthew L. Albert, Alain Michault, Kristen Monte, Dana L. Vanlandingham, Deborah J. Lenschow, Arnaud Fontanet, Scott W. Werneke, Fernando Arenzana-Seisdedos, Anjali Rohatgi, Washington University School of Medicine, University of Washington [Seattle], Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Pathogénie Virale Moléculaire, The University of Texas Medical Branch (UTMB), Kansas State University, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), D.J.L. was supported by a developmental award from NIH grant U54 AI05716007, a Pew Scholar Award, and an award from the Children's Discovery Institute. S.W. was supported by T32 AI00717231. M.L.A. acknowledges the L'Agence nationale de la recherché (ANR) for support of the research. Washington University Hybridoma Core facility and transgenic core facility was supported by NIH P30 AR048335. D.V. and S.H were in part supported by NIH AI R21 AI073389., We thank the Centre d'Immunologie Humaine and the CHIKV Task Force from the Institut Pasteur for support of this work and access to critical reagents. We also acknowledge Olivier Schwartz for helpful suggestions and for the careful review of the manuscript. We thank Kristen Monte and Charlotte Auriau for their outstanding expertise in animal care, and Stéphanie Thomas for support in sample transportation and filing of regulatory procedures., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and Vougny, Marie-Christine
Subjects: Ubiquitin-Activating Enzymes, MESH: Chikungunya Fever, MESH: Chikungunya virus/physiology, medicine.disease_cause, Mouse models, MESH: Animals, Newborn, Mice, MESH: Alphavirus Infections/diagnosis, Viral load, Conjugated proteins, MESH: Animals, Chikungunya, MESH: Cytokines/immunology, lcsh:QH301-705.5, Recombination, Genetic, 0303 health sciences, virus diseases, MESH: Alphavirus Infections/immunology, 3. Good health, Interferon Type I, Medicine, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Recombination, Genetic, Chikungunya infection, Chikungunya virus, medicine.drug, Research Article, Protein Binding, lcsh:Immunologic diseases. Allergy, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Ubiquitins/immunology, Immunology, MESH: Chikungunya virus/pathogenicity, Biology, Microbiology, Virus, Proinflammatory cytokine, MESH: Interferon Type I/immunology, 03 medical and health sciences, Immune system, MESH: Mice, Inbred C57BL, Virology, MESH: Interferon Type I/metabolism, MESH: Ubiquitins/metabolism, Genetics, medicine, Animals, Humans, MESH: Protein Binding, Alphavirus infection, Immune response, Molecular Biology, Ubiquitins, MESH: Mice, 030304 developmental biology, Retrospective Studies, MESH: Ubiquitin-Activating Enzymes/immunology, Innate immune system, MESH: Humans, 030306 microbiology, Alphavirus Infections, Neonates, MESH: Retrospective Studies, MESH: Ubiquitin-Activating Enzymes/metabolism, medicine.disease, Mice, Inbred C57BL, MESH: Alphavirus Infections/metabolism, Disease Models, Animal, Animals, Newborn, lcsh:Biology (General), Chikungunya Fever, Parasitology, Interferons, MESH: Disease Models, Animal, MESH: Cytokines/metabolism, lcsh:RC581-607, Interferon type I
Abstract: Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L−/− mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15−/− mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15−/− mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection., Author Summary Type I interferon plays a critical role in the host defense to viral infection. Signaling through the type I IFN receptor allows for the induction of hundreds of interferon stimulated genes (ISGs) that generate an antiviral state within host cells. The ubiquitin-like molecule ISG15 has been shown to play an important role during multiple viral infections, including influenza virus infection. To date, the ability of ISG15 to protect against viral infection has been shown to be dependent on its ability to covalently bind (or conjugate) to target proteins, including the binding of viral proteins. We investigated the importance of the type I interferon response and ISG15 conjugation in a neonatal model of Chikungunya virus infection, a re-emerging human pathogen in the Indian Ocean region. Remarkably, the role of ISG15 during CHIKV infection appears to be conjugation independent, suggesting a non-classical role for ISG15 during viral infection. Our data also suggests that ISG15 plays an immunoregulatory role, as opposed to having direct antiviral function. Our CHIKV model may provide an opportunity to identify a novel mechanism by which ISG15 contributes to the innate immune response to viral infection.
Published: 2011
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32. Neuro-glial crosstalk in inflammatory bowel disease

Author: L. Van Landeghem, Tor C. Savidge, Michel Neunlist, Arnaud Bourreille, Neunlist, Michel, Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes (UN), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Department of Gastroenterology, and The University of Texas Medical Branch (UTMB)
Subjects: Crohn's disease, business.industry, Inflammation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, Inflammatory bowel disease, Intestinal absorption, Enteric Nervous System, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Pathogenesis, Intestines, Immune system, Intestinal Absorption, Immunology, Internal Medicine, medicine, Humans, Enteric nervous system, medicine.symptom, business, Neuroglia
Abstract: International audience; Inflammatory bowel disease (IBD) is a multifactorial disease in which environmental, immune and genetic factors are involved in the pathogenesis. Although biological therapies (antibodies anti-tumour necrosis factor-alpha or anti-integrin) have considerably improved the symptoms and quality of life of IBD patients, some drawbacks have emerged limiting their long-term use. In addition, prevention of relapses and treatment of resistant ulcers remains a clinical challenge. In this context, a better understanding of the pathophysiology of IBD and the development of novel therapeutic intervention would benefit from further basic and preclinical research into the role of the cellular microenvironment and the interaction between its cellular constituents. In this context, the role of the enteric nervous system (ENS) in the regulation of the intestinal epithelial barrier (IEB) and the gut immune response has fuelled an increased interest in the last few years. Recent advances, summarized in this review, have highlighted the ENS as playing a key role in the control of IEB functions and gut immune homeostasis, and that alterations of the ENS could be directly associated in the development of IBD and its associated symptoms.
Published: 2008
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33. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate

Author: Ting Qian, Asle Aarsland, David N. Herndon, Melanie G. Cree, Béatrice Morio, Arthur P. Sanford, Ricki Y. Fram, Robert R. Wolfe, Jennifer J. Zwetsloot, University of Texas Medical Branch, Partenaires INRAE, East Carolina University, Shriners Hospitals for Children [Boston], Department of Cell Physiology, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre de Recherche en Nutrition Humaine, Department of Anesthesiology, and The University of Texas Medical Branch (UTMB)
Subjects: Blood Glucose, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Biopsy, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Double-Blind Method, Fenofibrate, Diabetes mellitus, Intensive care, Internal medicine, medicine, Humans, PPAR alpha, Myocardial infarction, Prospective Studies, Child, Muscle, Skeletal, 030304 developmental biology, Hypolipidemic Agents, 0303 health sciences, Trauma Severity Indices, business.industry, Insulin, 030208 emergency & critical care medicine, Glucose clamp technique, medicine.disease, 3. Good health, Metformin, Mitochondria, Muscle, Endocrinology, Treatment Outcome, Liver, Child, Preschool, Randomized Controlled Trial, Cardiology, Glucose Clamp Technique, Surgery, Animal studies, Insulin Resistance, business, Burns, medicine.drug, Follow-Up Studies
Abstract: Multiple studies have documented hyperglycemia and insulin resistance following trauma, myocardial infarction, stroke, or surgery.1–4 Both are of serious clinical concern, as hyperglycemia is associated with increased morbidity and mortality of critically ill, surgical, and burned patients.3–5 These outcome studies emphasize the importance of better understanding insulin resistance in this large patient population. Pediatric burns provide a unique model for studying acute onset insulin resistance, since the nature of the injury is severe and quantifiable and the timing of onset is exactly known. Further, lean children are much less likely to have preexisting comorbid conditions such as diabetes, or to have been taking medications prior to injury. We have recently demonstrated that mitochondrial oxidative function is impaired in burned children by more than 70% at 1 week postburn.6 A limited number of animal studies have found that mitochondrial genes, protein, and function are also decreased in skeletal muscle, liver, and cardiac muscle following burn injury.7–9 Similar findings were reported from the liver of patients who died after prolonged stays in intensive care for nonsurgical illness.10 In patients with type II diabetes, correlations between mitochondrial function and insulin sensitivity have been documented.11,12 These studies indicate that improving mitochondrial function may be a potential treatment target for improving insulin sensitivity. There are limited proven therapies for treating acute injury-induced insulin resistance. Insulin therapy to prevent hyperglycemia has been shown to reduce mortality and/or morbidity in intensive care patients, patients undergoing surgical procedures and in burns.4,10 However, intensive insulin therapy requires constant vigilance and does not alter the underlying pathology. One study found that metformin decreased muscle loss after burn,13 but other medications that are typically prescribed for treatment of insulin resistance have not been tested in these populations. PPAR-γ agonists, or thioglitazones, have been shown to improve insulin sensitivity in patients with diabetes.14 The mechanism of action apparently involves suppression of peripheral lipolysis and redistribution of triglyceride stores to subcutaneous fat cells.14 However, burned children often have a large amount of their subcutaneous triglyceride stores destroyed or removed, decreasing the availability for redistribution sites. Further, burn patients may be treated with the beta-blocking agent propranolol to reduce myocardial stress, which also suppresses lipolysis.15 Therefore, a PPAR-γ agonist would be anticipated to be redundant in children given propranolol. PPAR-α agonists have been shown in numerous animal studies and a few human studies to improve insulin sensitivity by enhancing mitochondrial function.16–18 We therefore hypothesized that PPAR-α agonism would stimulate mitochondrial function and improve insulin sensitivity in pediatric burn patients.
Published: 2007
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34. New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences

Author: Ernest A. Gould, Xavier de Lamballerie, Philippe Lemey, Antoine Nougairède, Shelley Cook, Rémi N. Charrel, Gregory Moureau, Naomi L. Forrester, Khasnatinov Ma, Andrew E. Firth, Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Life Sciences, The Natural History Museum [London] (NHM), Department of Microbiology and Immunology, Rega Institute, K.U. Leuven, Institute for Human Infections and Immunity and Department of Pathology, The University of Texas Medical Branch (UTMB), Centre for Ecology and Hydrology, Maclean Building, Division of Virology, University of Cambridge [UK] (CAM), and Lee, Young-Min
Subjects: BAGAZA VIRUS, Old World, Science, viruses, Molecular Sequence Data, GENUS FLAVIVIRUS, Genomics, Genome, Viral, INSECT-SPECIFIC FLAVIVIRUSES, Biology, Q1, WEST-NILE-VIRUS, complex mixtures, Genome, Evolution, Molecular, Open Reading Frames, Phylogenetics, NATURAL MOSQUITO POPULATION, DENGUE VIRUS, Phylogeny, Genetics, Translational frameshift, Multidisciplinary, Base Sequence, Phylogenetic tree, Flavivirus, Frameshifting, Ribosomal, virus diseases, NORTH-AMERICA, FUSING AGENT VIRUS, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, ENCEPHALITIS-VIRUS, Phylogeography, Biology and Microbiology, TICK-BORNE FLAVIVIRUSES, Evolutionary biology, Viral evolution, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Research Article
Abstract: To generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with Culex spp. mosquitoes. We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of flaviviruses whose evolutionary history, shows that different Culex-spp. associated flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses. We also discuss the significance of programmed ribosomal frameshifting in a central region of the polyprotein open reading frame in some mosquito-associated flaviviruses. ispartof: PLoS One vol:10 issue:2 ispartof: location:United States status: published
Published: 2015
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35. PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

Author: Ronald P. Mlcak, Dayoung Sun, Asle Aarsland, Béatrice Morio, Melanie G. Cree, G. Lynis Dohm, Ricki Y. Fram, Jennifer J. Zwetsloot, Ting Qian, Bradley R. Newcomer, Robert R. Wolfe, David N. Herndon, University of Texas Medical Branch, Partenaires INRAE, University of Alabama, Department of Finance, Shriners Hospitals for Children [Boston], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre de Recherche en Nutrition Humaine, East Carolina University, Department of Anesthesiology, and The University of Texas Medical Branch (UTMB)
Subjects: Agonist, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Peroxisome proliferator-activated receptor, Medicine (miscellaneous), lcsh:TX341-641, 030209 endocrinology & metabolism, 03 medical and health sciences, chemistry.chemical_compound, Acyl-CoA, 0302 clinical medicine, Insulin resistance, Internal medicine, medicine, Carnitine, lcsh:RC620-627, 030304 developmental biology, Diacylglycerol kinase, chemistry.chemical_classification, 0303 health sciences, Nutrition and Dietetics, Triglyceride, business.industry, Research, medicine.disease, 3. Good health, lcsh:Nutritional diseases. Deficiency diseases, Endocrinology, chemistry, lipids (amino acids, peptides, and proteins), business, lcsh:Nutrition. Foods and food supply, Intracellular, medicine.drug
Abstract: Article n.9 Open access : http://www.nutritionandmetabolism.com/content/4/1/9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17451602; International audience; BACKGROUND: Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat beta-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. METHODS: A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-alpha agonist treatment. RESULTS: Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-alpha agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-alpha treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-theta activation during hyper-insulinemia decreased significantly following PPAR-alpha treatment. CONCLUSION: PPAR-alpha agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.
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1. Type I IFN controls chikungunya virus via its action on nonhematopoietic cells

2. Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial

3. Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice

4. Excess all-cause mortality and COVID-19-related mortality:a temporal analysis in 22 countries, from January until August 2020

5. Pannexin-1 channel opening is critical for COVID-19 pathogenesis

6. Rational design of universal immunotherapy for TfR1-tropic arenaviruses

7. Antiviral activity of oleandrin and a defined extract of Nerium oleander against SARS-CoV-2

8. Resurgence of Ebola Virus in 2021 in Guinea Suggests a New Paradigm for Outbreaks

9. Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network

10. GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 5: Entomological aspects

11. GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 2: Epidemiological distribution of o'nyong-nyong virus

12. GloPID-R report on Chikungunya, O'nyong-nyong and Mayaro virus, part I: Biological diagnostics

13. NLRP3 inflammasome activation drives tau pathology

14. Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome

15. Meeting the challenge of tick-borne disease control: A proposal for 1000 Ixodes genomes

16. Changes in the Transmission Dynamic of Chikungunya Virus in Southeastern Senegal

17. rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences

18. Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa

19. Biochemistry and Molecular Biology of Flaviviruses

20. Assessing the epidemiological effect of wolbachia for dengue control

21. Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases

22. Chikungunya Outbreak in Kedougou, Southeastern Senegal in 2009-2010

23. Lactobacillus rhamnosus GG increases cyclooxygenase-2 expression and prostaglandin E2 secretion in colonic myofibroblasts via a MyD88-dependent mechanism during homeostasis

24. Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined with FOLFOX Chemotherapy in Patients with Metastatic Colorectal Cancer

25. Chikungunya Virus–Vector Interactions

26. The neuroimmune basis of fatigue

27. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements

28. The Global Virus Network: Challenging chikungunya

29. Chikungunya Virus Infections

30. Chikungunya Virus and the Global Spread of a Mosquito-Borne Disease

31. ISG15 is critical in the control of Chikungunya virus infection independent of UbE1L mediated conjugation

32. Neuro-glial crosstalk in inflammatory bowel disease

33. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate

34. New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences

35. PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

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35 results on '"The University of Texas Medical Branch ( UTMB )"'

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