Author: "Hélène Laude" - Searchworks@Jio Institute Digital Library Search Results

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1. Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans

Author: Francisco J. Martinez, Micheline Guillotte-Blisnick, Christèle Huon, Patrick England, Jean Popovici, Hélène Laude, Laurence Arowas, Marie-Noëlle Ungeheuer, Jenny M. Reimer, Darrick Carter, Steve Reed, Paushali Mukherjee, Virander S. Chauhan, and Chetan E. Chitnis
Subjects: Medicine, Science
Abstract: Abstract The invasion of reticulocytes by Plasmodium vivax merozoites is dependent on the interaction of the Plasmodium vivax Duffy Binding Protein (PvDBP) with the Duffy antigen receptor for chemokines (DARC). The N-terminal cysteine-rich region II of PvDBP (PvDBPII), which binds DARC, is a leading P. vivax malaria vaccine candidate. Here, we have evaluated the immunogenicity of recombinant PvDBPII formulated with the adjuvants Matrix-M and GLA-SE in mice. Analysis of the antibody responses revealed comparable ELISA recognition titres as well as similar recognition of native PvDBP in P. vivax schizonts by immunofluorescence assay. Moreover, antibodies elicited by the two adjuvant formulations had similar functional properties such as avidity, isotype profile and inhibition of PvDBPII-DARC binding. Furthermore, the anti-PvDBPII antibodies were able to block the interaction of DARC with the homologous PvDBPII SalI allele as well as the heterologous PvDBPII PvW1 allele from a Thai clinical isolate that is used for controlled human malaria infections (CHMI). The cross-reactivity of these antibodies with PvW1 suggest that immunization with the PvDBPII SalI strain should neutralize reticulocyte invasion by the challenge P. vivax strain PvW1.
Published: 2023
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2. T cell migration and effector function differences in familial adenomatous polyposis patients with APC gene mutations

Author: Céline Cuche, Marta Mastrogiovanni, Marie Juzans, Hélène Laude, Marie-Noëlle Ungeheuer, Daniel Krentzel, Maria Isabella Gariboldi, Daniel Scott-Algara, Marianne Madec, Sophie Goyard, Camille Floch, Gaëlle Chauveau-Le Friec, Pierre Lafaye, Charlotte Renaudat, Muriel Le Bidan, Christine Micallef, Sandrine Schmutz, Sébastien Mella, Sophie Novault, Milena Hasan, Darragh Duffy, Vincenzo Di Bartolo, and Andrés Alcover
Subjects: Adenomatous polyposis coli, APC, familial adenomatous polyposis, T cell activation, T cell migration, cytokines, Immunologic diseases. Allergy, RC581-607
Abstract: Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. Our recent work indicates that the APC protein is involved in various phases of both CD4 and CD8 T cells responses. This prompted us to investigate an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. We characterized the immune cell repertoire in peripheral blood and the capacity of immune cells to respond ex vivo to different stimuli either in whole blood or in purified T cells. A variety of experimental approaches were used, including, pultiparamater flow cytometry, NanosString gene expression profiling, Multiplex and regular ELISA, confocal microscopy and computer-based image analyis methods. We found that the percentage of several T and natural killer (NK) cell populations, the expression of several genes induced upon innate or adaptive immune stimulation and the production of several cytokines and chemokines was different. Moreover, the capacity of T cells to migrate in response to chemokine was consistently altered. Finally, immunological synapses between FAP cytotoxic T cells and tumor target cells were more poorly structured. Our findings of this pilot study suggest that mild but multiple immune cell dysfunctions, together with intestinal epithelial dysplasia in FAP subjects, may facilitate the long-term polyposis and colorectal tumor development. Although at an initial discovery phase due to the limited sample size of this rare disease cohort, our findings open new perspectives to consider immune cell abnormalities into polyposis pathology.
Published: 2023
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3. Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

Author: Danielle Perez-Bercoff, Hélène Laude, Morgane Lemaire, Oliver Hunewald, Valérie Thiers, Marco Vignuzzi, Hervé Blanc, Aurélie Poli, Zahir Amoura, Vincent Caval, Rodolphe Suspène, François Hafezi, Alexis Mathian, Jean-Pierre Vartanian, and Simon Wain-Hobson
Subjects: Medicine, Science
Abstract: Abstract APOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.
Published: 2021
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4. The ICAReB Platform: A Human Biobank for the 'Institut Pasteur' and Beyond

Author: Philippe Esterre, Amina Ait-Saadi, Laurence Arowas, Sophie Chaouche, Nicole Corre-Catelin, Christine Fanaud, Hélène Laude, Vesna Mellon, Valérie Monceaux, Gloria Morizot, Imène Najjar, Catherine Ottone, Blanca Liliana Perlaza, Blandine Rimbault, Linda Sangari, and Marie-Noëlle Ungeheuer
Subjects: biobanking, biospecimens, sample collection, cohort, healthy volunteers, Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: The ICAReB platform of Institut Pasteur provides access to human bio-resources for academic and private research teams worldwide, essentially in the fields of infection, immunity and neurosciences. More than 134,000 human quality controlled, duly annotated samples (mainly whole-blood derived products, but also stool, urine, saliva, swabs….), from both healthy and diseased cohorts with open, regulated access, are available upon request. Both clinical investigation and biobanking activities are certified following ISO 9001:2015 and NF S96-900:2011 standards, respectively. ICAReB is a member of PIBnet (Pasteur International Biobanking network), BIOBANQUES and BBMRI, the French and pan-european biobanking networks, respectively. Funding statement: Funds come from IP (facilities and staff), and from various funding organisms or agencies (for specific projects): ANR (French National Research funding Agency): 'OH!Ticks' project (see https://www.ohticks.fr/ 2017–2020) AP/HP ('Assistance Publique/Hôpitaux de Paris'): 'MonaLisa' (Multicentric Observational National Analysis on Listeriosis and Listeria) and 'ListeriaGEN' projects, 2009–2022 and 2015–2024, respectively AVIESAN (French National alliance for Life Sciences and Health). Study of the innate immunity and the microbial flora during aplasia ('PAMPA' project, 2013–2016) Bioaster (French 'Investissements d’Avenir' funding, Infectiology and Microbiology platform, Lyon-Paris, 2010–2020) Biomérieux (Lyon, France; cardio-vascular biomarker, 2013–2015) FRM (Medical Research Foundation): 'Hidradenitis Suppurativa' project (2011–2015) IBiSA (Biology, Health and Agronomics infrastructure) selection of ICAReB platform in 2009 INCA (National Institute for Cancer research): 'INECOC' project, 2009–2011 TOTAL foundation ('Afribiota' project on Environmental Pediatric Enteropathy, 2016-2020) WHO (for The WHO 'Human African Trypanosomiasis specimen Bank', 2008–2018, 2019–). Since three years, public-private relationships were proposed and research collaborations accepted with industrial partners, for example the Lyon-Paris ‘Technological Research Institute’ ('BioAster') following a national 'Investissements d’Avenir' program launched in 2012.
Published: 2020
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5. Investigation of viral etiology in potentially malignant disorders and oral squamous cell carcinomas in non-smoking, non-drinking patients.

Author: Philippe Pérot, Michaël Falguieres, Laurence Arowas, Hélène Laude, Jean-Philippe Foy, Patrick Goudot, Nicole Corre-Catelin, Marie-Noëlle Ungeheuer, Valérie Caro, Isabelle Heard, Marc Eloit, Antoine Gessain, Chloé Bertolus, and Nicolas Berthet
Subjects: Medicine, Science
Abstract: Head and neck squamous cell carcinomas (HNSCC) are the seventh most frequent cancers. Among HNSCCs, oral squamous cell carcinomas (OSCCs) include several anatomical locations of the oral cavity, but exclude the oropharynx. The known risk factors for OSCCs are mainly alcohol consumption and tobacco use for at least 75-80% of cases. In addition to these risk factors, Human papillomavirus (HPV) types 16 and 18, classified as high-risk (HR) HPV genotypes, are considered as risk factors for oropharyngeal cancers, but their role in the development of OSCC remains unclear. We tested the hypothesis of viral etiology in a series of 68 well-characterized OSCCs and 14 potentially malignant disorders (PMD) in non-smoking, non-drinking (NSND) patients using broad-range, sensitive molecular methodologies. Deep-sequencing of the transcriptome did not reveal any vertebrate virus sequences other than HPV transcripts, detected in only one case. In contrast, HPV DNA was detected in 41.2% (28/68) and 35.7% (5/14) of OSCC and PMD cases, respectively. Importantly, 90.9% (30/33) of these belonged to the Betapapillomavirus genus, but no viral transcripts were detected. Finally, high-throughput sequencing revealed reads corresponding to transcripts of the Trichomonas vaginalis virus (TVV), which were confirmed by RT-PCR in two OSCCs. Our results strongly suggest that Alphapapillomavirus genotypes classified as HR are not involved in the development of OSCCs in NSND patients and that known oncogenic infectious agents are absent in these specific OSCCs. Any possible direct or indirect role of Betapapillomavirus genus members and TVV in OSCCs remains speculative and requires further investigation.
Published: 2020
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6. Stepwise development of MAIT cells in mouse and human.

Author: Emmanuel Martin, Emmanuel Treiner, Livine Duban, Lucia Guerri, Hélène Laude, Cécile Toly, Virginie Premel, Anne Devys, Ivan C Moura, Florence Tilloy, Stéphane Cherif, Gabriella Vera, Sylvain Latour, Claire Soudais, and Olivier Lantz
Subjects: Biology (General), QH301-705.5
Abstract: Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)alpha (iTCRalpha) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanValpha7.2 antibody and MAIT cell-specific iTCRalpha and TCRbeta transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRalpha and TCRbeta transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%-4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and gammadelta T cells.
Published: 2009
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7. Complement-dependent mpox-virus-neutralizing antibodies in infected and vaccinated individuals

Author: Mathieu Hubert, Florence Guivel-Benhassine, Timothée Bruel, Françoise Porrot, Delphine Planas, Jessica Vanhomwegen, Aurélie Wiedemann, Sonia Burrel, Stéphane Marot, Romain Palich, Gentiane Monsel, Harouna Diombera, Sébastien Gallien, Jose Luis Lopez-Zaragoza, William Vindrios, Fabien Taieb, Sandrine Fernandes-Pellerin, Maurine Delhaye, Hélène Laude, Laurence Arowas, Marie-Noelle Ungeheuer, Laurent Hocqueloux, Valérie Pourcher, Thierry Prazuck, Anne-Geneviève Marcelin, Jean-Daniel Lelièvre, Christophe Batéjat, Yves Lévy, Jean-Claude Manuguerra, and Olivier Schwartz
Subjects: Virology, Parasitology, Microbiology
Published: 2023

8. The tumor suppressor adenomatous polyposis coli regulates T lymphocyte migration

Author: Marta Mastrogiovanni, Pablo Vargas, Thierry Rose, Céline Cuche, Elric Esposito, Marie Juzans, Hélène Laude, Amandine Schneider, Mathilde Bernard, Sophie Goyard, Charlotte Renaudat, Marie-Noëlle Ungeheuer, Jérôme Delon, Andrés Alcover, Vincenzo Di Bartolo, Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre-Gilles de Gennes pour la Microfluidique, BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), 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 Paris Cité (UPCité), This work was supported by grants from La Ligue Nationale contre le Cancer and Equipe Labellisée Ligue 2018 and institutional grants from Institut Pasteur and INSERM. UtechS Photonic BioImaging is supported by the National Research Agency (France BioImaging, ANR-10-INBS-04, Investments for the Future). M.M. is a scholar of the Pasteur Paris University International Doctoral Program, supported by the Institut Pasteur and the European Union Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement 665807 (COFUND-PASTEURDOC). M.M. is currently funded by 'Allocation doctorale 4ème année de thèse-La Ligue Contre Le Cancer.', ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), JEANNOT, FLORENCE, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID
Subjects: MESH: Adenomatous Polyposis Coli Protein, Multidisciplinary, MESH: Humans, MESH: Mutation, [SDV]Life Sciences [q-bio], Adenomatous Polyposis Coli Protein, MESH: Phenotype, MESH: Adenomatous Polyposis Coli, [SDV] Life Sciences [q-bio], Phenotype, Adenomatous Polyposis Coli, Cell Movement, Mutation, Humans, MESH: Cell Movement
Abstract: International audience; Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous polyposis (FAP) and colorectal cancer. Although its role in intestinal epithelial cells is well characterized, APC importance in T cell biology is ill defined. APC regulates cytoskeleton organization, cell polarity, and migration in various cell types. Here, we address whether APC plays a role in T lymphocyte migration. Using a series of cell biology tools, we unveiled that T cells from FAP patients carrying APC mutations display impaired adhesion and motility in constrained environments. We further dissected the cellular mechanisms underpinning these defects in APC-depleted CEM T cell line that recapitulate the phenotype observed in FAP T cells. We found that APC affects T cell motility by modulating integrin-dependent adhesion and cytoskeleton reorganization. Hence, APC mutations in FAP patients not only drive intestinal neoplasms but also impair T cell migration, potentially contributing to inefficient antitumor immunity.
Published: 2022

9. Broad-Range Papillomavirus Transcriptome as a Biomarker of Papillomavirus-Associated Cervical High-Grade Cytology

Author: Delphine Chrétien, Laurence Arowas, André Nazac, Jacques Marchetta, Isabelle Heard, Hélène Laude, Marc Eloit, Philippe Pérot, Thomas Hébert, Michaël Falguières, Anne-Gaelle Pourcelot, Anne Biton, Henri Marret, Marie-Christine Demazoin, Découverte de Pathogènes - Pathogen Discovery, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre National de Référence pour les Papillomavirus Humains - Génétique, Papillomavirus et Cancer Humain (CNR-HPV), Institut Pasteur [Paris], École nationale vétérinaire d'Alfort (ENVA), Supported by Institut Pasteur grants InnovDiag and Pasteur Innov., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Institut Pasteur [Paris] (IP), and École nationale vétérinaire - Alfort (ENVA)
Subjects: 0301 basic medicine, Uterine Cervical Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cytology, Biomarkers, Tumor, Humans, Medicine, Dna viral, Papillomaviridae, Early Detection of Cancer, Precancerous Cells, Vaginal Smears, business.industry, Papillomavirus Infections, virus diseases, Diagnostic test, Papanicolaou Test, Uterine Cervical Dysplasia, Predictive value, Cervical smears, female genital diseases and pregnancy complications, 3. Good health, 030104 developmental biology, Molecular Diagnostic Techniques, 030220 oncology & carcinogenesis, DNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cancer research, Molecular Medicine, Female, Neoplasm Grading, Triage, business
Abstract: International audience; Human Papillomaviruses (HPV) are responsible for over 99% of cervical cancers. Molecular diagnostic tests based on the detection of viral DNA or RNA have low Positive Predictive Values (PPV) for the identification of cancer or precancerous lesions. Triage with the Papanicolaou test lacks sensitivity and even when combined with molecular detection of high-risk HPV results in a significant number of unnecessary colposcopies. We have developed a broad range detection test of HPV transcripts to take a snapshot of the transcriptome of 16 high-risk or putative high-risk HPV in cervical lesions (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82). The purpose of this novel molecular assay is to detect and type HPV-positive samples and to determine a combination of HPV reads at certain specific viral spliced junctions that can better correlate with high-grade cytology, reflecting the presence of precancerous cells. In a proof-of-concept study conducted on 55 patients, starting from cervical smears, we have shown that (i) HPV RNA-Seq can detect papillomaviruses with performances comparable to a widely used HPV reference molecular diagnostic kit, and (ii) a combination of the number of sequencing reads at specific early vs late HPV transcripts can be used as a marker of high-grade cytology, with encouraging diagnostic performances as a triage test.
Published: 2019

10. Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

Author: Valérie Thiers, Aurélie Poli, Vincent Caval, François Hafezi, Morgane Lemaire, Hélène Laude, Hervé Blanc, Jean-Pierre Vartanian, Marco Vignuzzi, Danielle Perez-Bercoff, Simon Wain-Hobson, Alexis Mathian, Rodolphe Suspène, Zahir Amoura, Oliver Hunewald, Gestionnaire, Hal Sorbonne Université, Luxembourg Institute of Health (LIH), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], This work was supported by Fonds National de la Recherche du Luxembourg (INTER/Mobility/16/1154722/APO-SLE), by Ministère de l’Education et de la Recherche du Luxembourg and by Institut Pasteur Paris. FH was supported by FNR-PRIDE scheme (PRIDE/11012546/NEXTIMMUNE)., Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Programmed cell death, Science, [SDV]Life Sciences [q-bio], Cell, Immunology, Peripheral blood mononuclear cell, Polymorphism, Single Nucleotide, Gene Expression Regulation, Enzymologic, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Polymorphism (computer science), Genetics, Medicine, Humans, Lupus Erythematosus, Systemic, Telomerase reverse transcriptase, APOBEC Deaminases, Telomerase, Germ-Line Mutation, 030304 developmental biology, Cancer, 0303 health sciences, Multidisciplinary, Cell Death, business.industry, Interferon-alpha, Hydroxychloroquine, medicine.disease, 3. Good health, Up-Regulation, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: APOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.
Published: 2021

11. The Merkel Cell Polyomavirus: an oncogenic virus infecting humans

Author: Hélène, Laude
Abstract: The Merkel cell polyomavirus has been named after a rare type of skin cancer, Merkel cell carcinoma, in which the virus was identified in 2008. It belongs to a family that includes well-known carcinogenic viruses in animals. Five years later, data are now available on Merkel cell polyomavirus structure, genomic organization, protein functions and replication cycle although there is still a need of in vitro and in vivo models. Despite the ubiquitous aspect of the MCPyV infection, the identification of several tumour specific viral markers supports that Merkel cell polyomavirus is indeed an etiologic agent of Merkel cell carcinoma. Moreover, whereas some mechanisms previously described with others polyomavirus have been confirmed, some new interactions between cellular and viral proteins have been identified that pave the way to the understanding of the molecular mechanisms underlying cellular transformation. Finally, in a clinical perspective, Merkel cell polyomavirus research brings potential tools for diagnosis, prognosis evaluation and new therapeutic approaches to manage Merkel cell carcinoma, a severe disease the frequency of which is increasing.
Published: 2020

12. Investigation of viral etiology in potentially malignant disorders and oral squamous cell carcinomas in non-smoking, non-drinking patients

Author: Nicolas Berthet, Antoine Gessain, Jean-Philippe Foy, Michaël Falguières, Nicole Corre-Catelin, Marie-Noëlle Ungeheuer, Chloé Bertolus, Valérie Caro, Isabelle Heard, Patrick Goudot, Philippe Pérot, Laurence Arowas, Hélène Laude, Marc Eloit, Pérot, Philippe, Découverte de Pathogènes - Pathogen Discovery, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence pour les Papillomavirus Humains - Génétique, Papillomavirus et Cancer Humain (CNR-HPV), Institut Pasteur [Paris] (IP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [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), Service de Stomatologie et Chirurgie Maxillo-facial [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), École nationale vétérinaire - Alfort (ENVA), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The French Institut National du Cancer - INCa - had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], École nationale vétérinaire d'Alfort (ENVA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Epidemiology, Carcinogenesis, Cell, Artificial Gene Amplification and Extension, Alphapapillomavirus, Pathology and Laboratory Medicine, Polymerase Chain Reaction, law.invention, Transcriptome, 0302 clinical medicine, law, Genotype, Medicine and Health Sciences, Medicine, Papillomaviridae, Polymerase chain reaction, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multidisciplinary, Alcohol Consumption, Cancer Risk Factors, Smoking, Squamous Cell Carcinomas, Middle Aged, 3. Good health, medicine.anatomical_structure, Oncology, Medical Microbiology, 030220 oncology & carcinogenesis, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Carcinoma, Squamous Cell, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Mouth Neoplasms, Pathogens, Anatomy, Research Article, Adult, food.ingredient, Papillomaviruses, Alcohol Drinking, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Research and Analysis Methods, Microbiology, Carcinomas, Virus, 03 medical and health sciences, food, [SDV.CAN] Life Sciences [q-bio]/Cancer, Tongue, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Nutrition, Aged, Mouth, Betapapillomavirus, Biology and life sciences, business.industry, Papillomavirus Infections, Organisms, Human Papillomavirus, Cancers and Neoplasms, Reverse Transcriptase-Polymerase Chain Reaction, Diet, stomatognathic diseases, 030104 developmental biology, Medical Risk Factors, Cancer research, business, DNA viruses, Digestive System
Abstract: International audience; Head and neck squamous cell carcinomas (HNSCC) are the seventh most frequent cancers. Among HNSCCs, oral squamous cell carcinomas (OSCCs) include several anatomical locations of the oral cavity, but exclude the oropharynx. The known risk factors for OSCCs are mainly alcohol consumption and tobacco use for at least 75-80% of cases. In addition to these risk factors, Human papillomavirus (HPV) types 16 and 18, classified as high-risk (HR) HPV genotypes, are considered as risk factors for oropharyngeal cancers, but their role in the development of OSCC remains unclear. We tested the hypothesis of viral etiology in a series of 68 well-characterized OSCCs and 14 potentially malignant disorders (PMD) in non-smoking, non-drinking (NSND) patients using broad-range, sensitive molecular methodologies. Deep-sequencing of the transcriptome did not reveal any vertebrate virus sequences other than HPV transcripts, detected in only one case. In contrast, HPV DNA was detected in 41.2% (28/68) and 35.7% (5/14) of OSCC and PMD cases, respectively. Importantly, 90.9% (30/33) of these belonged to the Betapapillomavirus genus, but no viral transcripts were detected. Finally, high-throughput sequencing revealed reads corresponding to transcripts of the Trichomonas vaginalis virus (TVV), which were confirmed by RT-PCR in two OSCCs. Our results strongly suggest that Alphapapillomavirus genotypes classified as HR are not involved in the development of OSCCs in NSND patients and that known oncogenic infectious agents are absent in these specific OSCCs. Any possible direct or indirect role of Betapapillomavirus genus members and TVV in OSCCs remains speculative and requires further investigation.
Published: 2020

13. The ICAReB Platform: A Human Biobank for the Institut Pasteur and Beyond

Author: Gloria Morizot, Nicole Corre-Catelin, Linda Sangari, Catherine Ottone, Vesna Mellon, Christine Fanaud, Laurence Arowas, Philippe Esterre, Hélène Laude, Valérie Monceaux, Blanca Liliana Perlaza, Amina Ait-Saadi, Sophie Chaouche, Marie-Noëlle Ungeheuer, Imène Najjar, and Blandine Rimbault
Subjects: 0301 basic medicine, Infectiology, Immunology, Genetics, lcsh:Medicine, Medicine (miscellaneous), Library science, Health Informatics, Certification, sample collection, lcsh:Computer applications to medicine. Medical informatics, Biochemistry, Genetics and Molecular Biology (miscellaneous), Technological research, 03 medical and health sciences, biobanking, 0302 clinical medicine, Health Information Management, Clinical investigation, biospecimens, Healthy volunteers, Funding Agency, lcsh:R, cohort, Cell Biology, healthy volunteers, Biobank, 030104 developmental biology, 030220 oncology & carcinogenesis, lcsh:R858-859.7, Sample collection
Abstract: The ICAReB platform of Institut Pasteur provides access to human bio-resources for academic and private research teams worldwide, essentially in the fields of infection, immunity and neurosciences. More than 134,000 human quality controlled, duly annotated samples (mainly whole-blood derived products, but also stool, urine, saliva, swabs….), from both healthy and diseased cohorts with open, regulated access, are available upon request. Both clinical investigation and biobanking activities are certified following ISO 9001:2015 and NF S96-900:2011 standards, respectively. ICAReB is a member of PIBnet (Pasteur International Biobanking network), BIOBANQUES and BBMRI, the French and pan-european biobanking networks, respectively. Funding statement: Funds come from IP (facilities and staff), and from various funding organisms or agencies (for specific projects): ANR (French National Research funding Agency): 'OH!Ticks' project (see https://www.ohticks.fr/ 2017–2020) AP/HP ('Assistance Publique/Hôpitaux de Paris'): 'MonaLisa' (Multicentric Observational National Analysis on Listeriosis and Listeria) and 'ListeriaGEN' projects, 2009–2022 and 2015–2024, respectively AVIESAN (French National alliance for Life Sciences and Health). Study of the innate immunity and the microbial flora during aplasia ('PAMPA' project, 2013–2016) Bioaster (French 'Investissements d’Avenir' funding, Infectiology and Microbiology platform, Lyon-Paris, 2010–2020) Biomérieux (Lyon, France; cardio-vascular biomarker, 2013–2015) FRM (Medical Research Foundation): 'Hidradenitis Suppurativa' project (2011–2015) IBiSA (Biology, Health and Agronomics infrastructure) selection of ICAReB platform in 2009 INCA (National Institute for Cancer research): 'INECOC' project, 2009–2011 TOTAL foundation ('Afribiota' project on Environmental Pediatric Enteropathy, 2016-2020) WHO (for The WHO 'Human African Trypanosomiasis specimen Bank', 2008–2018, 2019–). Since three years, public-private relationships were proposed and research collaborations accepted with industrial partners, for example the Lyon-Paris ‘Technological Research Institute’ ('BioAster') following a national 'Investissements d’Avenir' program launched in 2012.
Published: 2020

14. The rabbit as an orthologous small animal model for APOBEC3A oncogenesis

Author: Michel Henry, Mohamed S. Bouzidi, Xiongxiong Li, Hélène Laude, Vincent Caval, Florence Jamet, Rodolphe Suspène, Jean-Pierre Vartanian, Simon Wain-Hobson, Rétrovirologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Lanzhou Institute of Biological Products Co. Ltd. (LIBP), This work was supported by funds from the Institut Pasteur and Centre National de la Recherche Scientifique (CNRS). Hélène Laude, Vincent Caval and Mohamed Salah Bouzidi were supported by the 'Assistance Publique des Hôpitaux de Paris', OSEO (FUI AAP12), and the Ligue Nationale contre le Cancer (GB/MA/CD-11283) respectively, Xiong Xiong Li was supported by a stipend from Lanzhou Institute of Biological Products Co., Ltd (LIBP), subsidiary company of China National Biotec Group Company Limited (CNBG) and by a stipend from the Pasteur - Paris University (PPU) International PhD program., We thank Dr. Robin Lombard from Miltenyi Biotec for his help in setting up the FRET-FACS assay, Rétrovirologie moléculaire - Molecular Retrovirology, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, APOBEC3A Gene, rabbit, Locus (genetics), [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, chemistry.chemical_compound, cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, APOBEC3A, Gene, cytidine deaminase, Genetics, 030102 biochemistry & molecular biology, animal model, Cytidine, Cytidine deaminase, 3. Good health, Nuclear DNA, genomic DNA, 030104 developmental biology, Oncology, chemistry, Research Paper
Abstract: // Helene C. Laude 1 , Vincent Caval 1 , Mohamed S. Bouzidi 1 , Xiongxiong Li 1, 2 , Florence Jamet 1 , Michel Henry 1 , Rodolphe Suspene 1 , Simon Wain-Hobson 1 and Jean-Pierre Vartanian 1 1 Molecular Retrovirology Unit, Institut Pasteur, CNRS UMR 3569, France 2 Lanzhou Institute of Biological Products Co., Ltd (LIBP), subsidiary company of China National Biotec Group Company Limited (CNBG), Lanzhou 730046, China Correspondence to: Jean-Pierre Vartanian, email: jean-pierre.vartanian@pasteur.fr Keywords: rabbit; animal model; APOBEC3A; cytidine deaminase; cancer Received: March 15, 2018 Accepted: May 24, 2018 Published: June 12, 2018 ABSTRACT APOBEC3 are cytidine deaminases that convert cytidine to uridine residues. APOBEC3A and APOBEC3B enzymes able to target genomic DNA are involved in oncogenesis of a sizeable proportion of human cancers. While the APOBEC3 locus is conserved in mammals, it encodes from 1–7 genes. APOBEC3A is conserved in most mammals, although absent in pigs, cats and throughout Rodentia whereas APOBEC3B is restricted to the Primate order. Here we show that the rabbit APOBEC3 locus encodes two genes of which APOBEC3A enzyme is strictly orthologous to human APOBEC3A. The rabbit enzyme is expressed in the nucleus and the cytoplasm, it can deaminate cytidine, 5-methcytidine residues, nuclear DNA and induce double-strand DNA breaks. The rabbit APOBEC3A enzyme is negatively regulated by the rabbit TRIB3 pseudokinase protein which is guardian of genome integrity, just like its human counterpart. This indicates that the APOBEC3A/TRIB3 pair is conserved over approximately 100 million years. The rabbit APOBEC3A gene is widely expressed in rabbit tissues, unlike human APOBEC3A . These data demonstrate that rabbit could be used as a small animal model for studying APOBEC3 driven oncogenesis.
Published: 2018

15. Prevalence and Risk Factors for Anal Human Papillomavirus Infection in Human Immunodeficiency Virus–Positive Men Who Have Sex with Men

Author: Lionel Piroth, P Tattevi, J-M Didelot, I Heard, Emmanuelle Ressiot, Pialoux, H Njatonirina, Tristan Ferry, J-D Combes, G M Clifford, Michaël Falguières, Jean-François Fléjou, Isabelle Heard, Jacques Reynes, Petrov Sanchez, G Maincent, Annie Lion, M Landon, Patey O, Jean-Damien Combes, Catherine Tamalet, L Marchand, Jean-Michel Didelot, Isabelle Etienney, T Ferry, Ana Canestri, F Le Breton, Cédric Arvieux, I Poizot-Martin, Laurent Siproudhis, L Piroth, I. Etienney, H Fischer, Gary M. Clifford, Olivier Patey, J-F Flejou, A-C Lesage, N Hoyau, S. Radenne, Sébastien Henno, Hélène Laude, J Del Grande, Lucie Marchand, Costes-Martineau, Isabelle Poizot-Martin, Herrada, Anthony, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre National de Référence pour les Papillomavirus - Rétrovirologie moléculaire - Génétique,Papillomavirus et Cancer humain, Institut Pasteur [Paris] (IP), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies infectieuses et tropicales [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Intercommunal Villeneuve-Saint-Georges (CHIV), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d'Anatomie et cytologie pathologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Dpt proctologie [CHU Croix St Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, This work was sponsored and funded by France Recherche Nord et Sud Sida-HIV et Hépatites (ANRS) [Convention No. 14730]., L. P. has received funding from Gilead, Janssen, MSD, and Viiv Healthcare for travel/accommodations/meeting expenses during the past 36 months not related to the submitted work. I. P. M. has received funding from Gilead, BMS, and Abbvie for board membership, from Gilead, MSD, and BMS as payment for lectures, including service on speakers bureaus, and from bms for travel/accommodations/meeting expenses during the past 36 months not related to the submitted work. All other authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., The ANRS EP57 APACHES study group would like to thank Marie Abrivard, Laurence Arowas, Sarah Azouaou, Véronique Chabanis, Sophie Circosta, Claude Crisol, Marie-Christine Demazoin, Anne Dumont, Susan Gamon, Philippine Gason, Damien Georges, Sandrine Gohier, Sophie Guillot, Alena Ivanova, Anne-Sophie Jouault, Hélène Laroche, Lydia Leger, Karine Lelandais, Emmanuelle Norguet, Sadia Medaouri, Stanislas Ogoudjobi, Enora Ouamara-Digue, Christelle Paul, Maja Ratajczak, Anne-Suzel Ritleng, Jennifer Rohan, Typhaine Thomas, Jérôme Vignat, Olivia Zaegel, and members of TRT-5. They are extremely grateful to all participants., Institut Pasteur [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP]
Subjects: medicine.medical_specialty, men who have sex with men, Men who have sex with men, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Immunology and Allergy, Anal cancer, 030212 general & internal medicine, anal canal, Prospective cohort study, human papillomavirus, Genotyping, high-resolution anoscopy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, human immunodeficiency virus, business.industry, HPV infection, Anoscopy, virus diseases, Odds ratio, 16. Peace & justice, medicine.disease, Confidence interval, female genital diseases and pregnancy complications, 3. Good health, Infectious Diseases, 030220 oncology & carcinogenesis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: A correction has been published:The Journal of Infectious Diseases, Volume 218, Issue 8, 15 October 2018, Page 1350, https://doi.org/10.1093/infdis/jiy315; International audience; Background:We assessed prevalence and risk factors for anal human papillomavirus (HPV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), who are at high-risk of HPV-related anal cancer.Methods:APACHES is a multicentric, prospective study of anal HPV infection and lesions in HIV-positive MSM aged ≥35 years. At baseline, participants underwent anal swabs for HPV and cytology, plus high-resolution anoscopy. High-risk HPV (HR-HPV) was tested by Cobas4800, with genotyping of HR-HPV positives by PapilloCheck.Results:Among 490 participants, prevalence of HPV16 and HR-HPV was 29% and 70%, respectively, and did not differ significantly by age, sexual behavior, or markers of HIV or immune deficiency. Smoking was the only, albeit weak (odds ratio, 1.8; 95% confidence interval, 1.2-2.7), predictor of HR-HPV. High-risk HPV and HPV16 prevalence increased strongly with anal diagnosis severity, both by worse cytological/histological (composite) diagnosis at APACHES baseline and worse historical diagnosis. HPV16 rose from 19% among participants who were negative for lesions to 63% among participants with high-grade lesions. In contrast, non-HPV16 HR-HPVs were less prevalent in high-grade (37%) than negative (64%) composite diagnosis, and their causal attribution was further challenged by multiple HPV infections.Conclusions:Human papillomavirus 16 is ubiquitously frequent among human immunodeficiency virus -positive men having sex with men, and more strongly associated with high-grade anal lesions than other high-risk types, confirming it as a target for anal cancer prevention.
Published: 2018

16. Sérologie anti-antigène T du polyomavirus de Merkel dans la surveillance des patients ayant un carcinome de Merkel : étude rétrospective multicentrique

Author: Serge Guyétant, G. Bens, Nathalie Beneton, E. Maubec, Thibault Kervarrec, M.-F. Avril, Monica Dinulescu, A. Blom, B. Dréno, Nicolas Dupin, Françoise Arnold, Y. Le Corre, F. Aubin, E. Wierzbicka-Hainaut, Hélène Laude, Pauline Gaboriaud, S. Giraud, Anne Le Touze, and Mahtab Samimi
Subjects: Dermatology
Abstract: Introduction Le carcinome de Merkel est un cancer neuroendocrine cutane rare mais agressif. Le principal agent causal est le polyomavirus de Merkel decouvert en 2008. Il a ete montre que les anticorps seriques diriges contre les antigenes T du polyomavirus de Merkel etaient specifiques des patients ayant un carcinome de Merkel. Il n’existe actuellement aucune recommandation concernant la surveillance biologique des patients alors qu’il semble que les titres d’anticorps anti-antigene T sont associes a la masse tumorale. L’objectif de cette etude etait d’evaluer si l’evolution des titres seriques d’anticorps anti-antigene T etait associee a l’evolution de la maladie au cours du suivi, et pouvait donc constituer un outil de surveillance ou « monitoring serologique ». Patients et methodes Nous avons realise une etude retrospective multicentrique chez des patients atteints de carcinome de Merkel entre fevrier 2008 et janvier 2018, ayant eu une serologie anti-antigene T au diagnostic initial (0-3mois) et au moins une autre serologie anti-antigene T apres 6 mois de suivi. Une technique ELISA permettait d’evaluer les titres d’anticorps anti-antigene T. L’augmentation ou la decroissance des titres etait consideree significative lorsqu’il existait une difference d’au moins deux dilutions des titres. Resultats Parmi les 156 patients ayant eu une serologie anti-antigene T au moment de la prise en charge initiale (0-3 mois suivant le diagnostic), 83 patients (incluant 41 seronegatifs et 42 seropositifs) avaient egalement eu au moins une autre evaluation serologique 6 mois apres le diagnostic. Dans le groupe seronegatif au diagnostic initial (n = 41), la detection de novo d’anticorps anti-antigene T au cours du suivi etait specifique d’une recidive (Sp = 100 %) mais peu sensible (Se = 23,8 %). Dans le groupe seropositif au diagnostic initial (n = 42), nous avons identifie 3 patterns A, B et C d’evolution des titres d’anticorps anti-antigene T au cours du suivi. L’ensemble des patients presentant des taux decroissants d’anticorps a 6 mois avec une seronegativite persistante au cours du suivi (pattern A, n = 18) etait en remission. Concernant les patterns B (decroissance initiale des anticorps avec persistance ou majoration au cours du suivi, n = 9) ou C (absence de decroissance des anticorps, n = 15), la persistance ou l’augmentation des titres apres 6 mois du diagnostic initial evoquait une evolution defavorable du carcinome de Merkel avec une sensibilite de 100 % et une specificite de 62,1 %. Discussion Notre etude suggere que la serologie anti-antigene T est un marqueur biologique utile dans le suivi des patients ayant un carcinome de Merkel. Realisee au diagnostic initial, puis regulierement au cours du suivi, elle permettrait de mettre en evidence les recidives/progressions.
Published: 2018

17. Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma

Author: Serge Guyétant, Flore Rozenberg, A. Carlotti, Eric Estève, Martine Avenel-Audran, Gérard Lorette, Eve Maubec, Antoine Touzé, François Aubin, Mahtab Samimi, E. Wierzbicka-Hainaut, Nicolas Dupin, Nathalie Beneton, L. Molet, Marie-Françoise Avril, C. Gardair, Hélène Laude, M. Baudin, Pierre Coursaget, Maxime Fleury, L. Gouguet, Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Groupe d'Etude des Interactions Hôte-Parasite (GEIHP), Université d'Angers (UA), Laboratoire d'Oncologie Virale, Centre National de la Recherche Scientifique (CNRS), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Département de dermatologie, CHU Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de dermatologie (CH Le Mans), Centre Hospitalier Le Mans (CH Le Mans), Service de dermatologie (CHRU Besançon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Calcul Thermodynamique, Institut de Mécanique et d'Ingénierie de Bordeaux (I2M), École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Francois Rabelais [Tours], Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de dermatologie [CH Le Mans], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Skin Neoplasms, [SDV]Life Sciences [q-bio], Merkel cell polyomavirus, Kaplan-Meier Estimate, Gastroenterology, Serology, 030207 dermatology & venereal diseases, 0302 clinical medicine, Merkel cell carcinoma, Antigens, Viral, Tumor, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, education.field_of_study, T-Ag antibodies, biology, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Oncovirus, Adult, medicine.medical_specialty, Population, Enzyme-Linked Immunosorbent Assay, Dermatology, Risk Assessment, 03 medical and health sciences, Antigen, Internal medicine, Biomarkers, Tumor, Carcinoma, medicine, Humans, education, Aged, Polyomavirus Infections, VP1 antibodies, business.industry, medicine.disease, biology.organism_classification, Carcinoma, Merkel Cell, Tumor Virus Infections, Immunology, biology.protein, Capsid Proteins, Neoplasm Recurrence, Local, business
Abstract: International audience; Merkel cell polyomavirus (MCPyV) is the main etiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T-antigens) have been reported specifically in patients with MCC. The primary aim of this study was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. Serum T-antigen and VP1 antibodies were assessed by ELISA using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. Low levels of VP1 antibodies at baseline (
Published: 2016

18. Arsenic Trioxide Prevents Murine Sclerodermatous Graft-versus-Host Disease

Author: Bernard Weill, Wioleta Marut, Frédéric Batteux, Amélie Servettaz, Hélène Laude, Niloufar Kavian, Carole Nicco, and Christiane Chéreau
Subjects: Male, Acute promyelocytic leukemia, medicine.medical_treatment, Immunology, Graft vs Host Disease, Hematopoietic stem cell transplantation, medicine.disease_cause, Arsenicals, Mice, Random Allocation, chemistry.chemical_compound, Arsenic Trioxide, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, Arsenic trioxide, Bone Marrow Transplantation, Mice, Inbred BALB C, Scleroderma, Systemic, business.industry, Oxides, medicine.disease, Fibrosis, Mice, Inbred C57BL, Transplantation, Disease Models, Animal, Graft-versus-host disease, medicine.anatomical_structure, chemistry, Chronic Disease, Female, Bone marrow, business, Spleen, Oxidative stress
Abstract: Chronic graft-versus-host disease (GVHD) follows allogeneic hematopoietic stem cell transplantation. It results from alloreactive processes induced by minor MHC incompatibilities triggered by activated APCs, such as plasmacytoid dendritic cells (pDCs), and leading to the activation of CD4 T cells. Therefore, we tested whether CD4+ and pDCs, activated cells that produce high levels of reactive oxygen species, could be killed by arsenic trioxide (As2O3), a chemotherapeutic drug used in the treatment of acute promyelocytic leukemia. Indeed, As2O3 exerts its cytotoxic effects by inducing a powerful oxidative stress that exceeds the lethal threshold. Sclerodermatous GVHD was induced in BALB/c mice by body irradiation, followed by B10.D2 bone marrow and spleen cell transplantation. Mice were simultaneously treated with daily i.p. injections of As2O3. Transplanted mice displayed severe clinical symptoms, including diarrhea, alopecia, vasculitis, and fibrosis of the skin and visceral organs. The symptoms were dramatically abrogated in mice treated with As2O3. These beneficial effects were mediated through the depletion of glutathione and the overproduction of H2O2 that killed activated CD4+ T cells and pDCs. The dramatic improvement provided by As2O3 in the model of sclerodermatous GVHD that associates fibrosis with immune activation provides a rationale for the evaluation of As2O3 in the management of patients affected by chronic GVHD.
Published: 2012

19. Contents Vol. 221, 2010

Author: Luca Borradori, L. Toutous-Trellu, Konstantinos I. Gourgoulianis, Thomas Bieber, Johan Chanal, T. Passeron, B.V. Stimec, Agnès Carlotti, P. Mandich, M. Kostaki, Natalie Ortega-Zilic, Shigetsuna Komatsu, Clarissa Huber, B. Ferrando, J. Boyle, Yoko Kano, A. Parodi, A.Y. Finlay, M. Lahfa, K.E. McKenna, B. Burger, J.P. Lacour, Carine Houriet, V. Hall, X.C. Pham, Nadège Wallet-Faber, N. Sebbag, Stephan Koehne-Voss, Jaume Alijotas-Reig, Satz Mengensatzproduktion, Diamant Thaçi, U. Darsow, J.H.D. Fasel, Nedzmidin Pelivani, Hajime Iizuka, V. Fausti, F.M. Hajjaj, Jürg Hafner, Victor Garcia-Gimenez, Natalia Garcia-Aranda, J.P. Tolland, Ori Rogowski, Thomas Hunziker, Felix Waldmeier, Takashi Shibuya, Julia Hanfland, Amir Gal-Oz, M. Grosber, Severin Läuchli, J. Mazereeuw-Hautier, P. Itin, Ichiro Takahashi, Katrin Baumann Conzett, Michael Swartzon, Roland Kaufmann, M. Becker, M.K.A. Basra, Tetsuo Shiohara, Hélène Laude, Francesc Miró-Mur, Noriko Aota Sato, A.M. Skaria, Shin Iinuma, Zoe Daniil, S.G. Plötz, B. Pasini, Akemi Ishida-Yamamoto, V. Piguet, Marie-Françoise Avril, Suzanne Hauffe, Masaru Honma, J. Kohlhase, L. Bruckner-Tuderman, G. Kaya, N. Cardot-Leccia, C. Has, Irene Planells-Romeu, C. Bulai Livideanu, Eckart Haneke, Nicolas Dupin, B.A. Aigner, Daniele Torchia, Shinichi Tobisawa, D. Salomon, Miquel Vilardell-Tarrés, Druck Reinhardt Druck Basel, Lars E. French, H. Montaudié, Foteini Malli, F. Rongioletti, A. Volz, J.S. Elborn, Kirstin Sippel, Shmuel Kivity, J. Ring, Rudolf Happle, M.S. Salek, C. Paul, and Dieter Mayer
Subjects: Dermatology
Published: 2010

20. Molecular basis of the attenuated phenotype of human APOBEC3B DNA mutator enzyme

Author: Vincent Caval, Hélène Laude, Marie-Charlotte Dumargne, Anu Bashamboo, Rodolphe Suspène, Jean-Pierre Vartanian, Mohamed S. Bouzidi, Simon Wain-Hobson, Thomas Krey, Rétrovirologie Moléculaire, Institut Pasteur [Paris] (IP), Génétique du Développement humain - Human developmental genetics, Virologie Structurale, Institut Pasteur, INCa and La Ligue Nationale contre le Cancer, and OSEO (FUI AAP12 to V.C). Funding for open access charge: Molecular Retrovirology Unit, Pasteur Institute.
Subjects: MESH: Minor Histocompatibility Antigens, MESH: Mutation, [SDV]Life Sciences [q-bio], Mutant, MESH: DNA Breaks, Double-Stranded, Biology, medicine.disease_cause, MESH: Phenotype, Quail, Cell Line, Minor Histocompatibility Antigens, MESH: Macaca mulatta, chemistry.chemical_compound, MESH: Protein Structure, Tertiary, Cytidine Deaminase, Genetics, medicine, Animals, Humans, DNA Breaks, Double-Stranded, MESH: Animals, MESH: Proteins, MESH: RNA Editing, APOBEC3A, Gene, Molecular Biology, MESH: Cytidine Deaminase, chemistry.chemical_classification, Mutation, MESH: Humans, MESH: Quail, Proteins, Cytidine, Cytidine deaminase, Macaca mulatta, Protein Structure, Tertiary, MESH: Cell Line, Enzyme, Phenotype, chemistry, MESH: HeLa Cells, RNA Editing, DNA, HeLa Cells
Abstract: International audience; The human APOBEC3A and APOBEC3B genes (A3A and A3B) encode DNA mutator enzymes that deaminate cytidine and 5-methylcytidine residues in single-stranded DNA (ssDNA). They are important sources of mutations in many cancer genomes which show a preponderance of CG->TA transitions. Although both enzymes can hypermutate chromosomal DNA in an experimental setting, only A3A can induce double strand DNA breaks, even though the catalytic domains of A3B and A3A differ by only 9% at the protein level. Accordingly we sought the molecular basis underlying A3B attenuation through the generation of A3A-A3B chimeras and mutants. It transpires that the N-terminal domain facilitates A3B activity while a handful of substitutions in the catalytic C-terminal domain impacting ssDNA binding serve to attenuate A3B compared to A3A. Interestingly, functional attenuation is also observed for the rhesus monkey rhA3B enzyme compared to rhA3A indicating that this genotoxic dichotomy has been selected for and maintained for some 38 million years. Expression of all human ssDNA cytidine deaminase genes is absent in mature sperm indicating they contribute to somatic mutation and cancer but not human diversity.
Published: 2015

21. Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients

Author: Martine Avenel-Audran, Nicolas Dupin, Serge Guyétant, Flore Rozenberg, M.-F. Avril, E Le Bidre, Pierre Coursaget, C. Gardair, Audrey Carpentier, Mahtab Samimi, A. Carlotti, Françoise Arnold, Antoine Touzé, François Aubin, Laurent Machet, Hélène Laude, Gérard Lorette, Eve Maubec, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), EA1833, Service de Dermatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Université Francois Rabelais [Tours], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ligue Contre le Cancer, Institut National de la Recherche Agronomique (INRA)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Adult, Male, Oncology, Pathology, medicine.medical_specialty, Skin Neoplasms, [SDV]Life Sciences [q-bio], Merkel cell polyomavirus, Dermatology, Calcitriol receptor, vitamin D deficiency, Metastasis, Cohort Studies, Internal medicine, Vitamin D and neurology, Humans, Medicine, Vitamin D, Aged, Aged, 80 and over, biology, business.industry, Merkel cell carcinoma, Cancer, food and beverages, Middle Aged, Vitamin D Deficiency, medicine.disease, biology.organism_classification, 3. Good health, Carcinoma, Merkel Cell, Treatment Outcome, Infectious Diseases, Receptors, Calcitriol, Immunohistochemistry, Female, business
Abstract: Background Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels
Published: 2014

22. Trichodysplasia spinulosa associated with lupus

Author: Agnès Carlotti, Flore Rozenberg, Marie Cécile Vacher Lavenu, Laurence Brudy Gulphe, Nicolas Dupin, Hélène Laude, and Anissa Moktefi
Subjects: Adult, Trichodysplasia spinulosa, Pathology, medicine.medical_specialty, Dermatology, Real-Time Polymerase Chain Reaction, Pathology and Forensic Medicine, law.invention, chemistry.chemical_compound, law, Eosinophilic, medicine, Humans, Lupus Erythematosus, Systemic, Pathological, Polymerase chain reaction, Polyomavirus Infections, Systemic lupus erythematosus, Lupus erythematosus, business.industry, General Medicine, medicine.disease, Trichodysplasia, chemistry, DNA, Viral, Female, business, Hair Diseases, Cidofovir
Abstract: Trichodysplasia spinulosa (TS) is a unique clinical and histological entity described in immunosuppressed patients. The recent discovery of genomic DNA from a new Polyomavirus named trichodysplasia spinulosa-associated Polyomavirus in TS lesions and good clinical response to cidofovir strengthens the hypothesis of a viral etiology for the disease. The authors report a case of TS associated with lupus erythematosus in a 26-year-old woman with no history of transplant, hemopathy, or cyclosporine treatment. The patient developed a progressive worsening eruption composed of confluent papules and spiky filiform excrescences concentrated in the midfacial area. Pathological features were characterized by aberrant distended and abnormally maturated hair follicles with sheets of eosinophilic cells containing large purple granules, and the presence of trichodysplasia spinulosa-associated Polyomavirus DNA was confirmed by polymerase chain reaction. This case is the first description in a nontransplanted lupus patient without underlying hemopathy.
Published: 2013

23. The case | Post-tranplant allograft dysfunction

Author: Christophe Legendre, Marion Rabant, Alyette Duquesne, Marianne Leruez, O. Aubert, Flore Rozenberg, Louise Galmiche, Anne Scemla, Hélène Laude, and Rebecca Sberro-Soussan
Subjects: Adult, Male, medicine.medical_specialty, Basiliximab, Anti-HIV Agents, Biopsy, HIV Infections, Mycophenolate, Kidney, Gastroenterology, Zidovudine, Predictive Value of Tests, Internal medicine, Medicine, Humans, Didanosine, Polyomavirus Infections, business.industry, Lopinavir, Immunohistochemistry, JC Virus, Kidney Transplantation, Tacrolimus, Tumor Virus Infections, Treatment Outcome, Nephrology, Immunology, HIV-2, Etiology, Kidney Failure, Chronic, Ritonavir, business, Immunosuppressive Agents, medicine.drug
Abstract: A 43-year-old man treated for human immunodeficiency virus type 2 (HIV2) with end-stage renal disease of unknown etiology received a deceased-donor renal transplant. He was treated with zidovudine, didanosine, lopinavir, and ritonavir. He received induction therapy with basiliximab. The immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. The patient also received intravenous immunoglobulin (four cycles of 2 g/kg) because of donor-specific antibodies (DSA) (A31 MFI: 1808) at day 0.
Published: 2013

24. Anogenital pseudotumoral herpes and HIV infection: a new challenge for diagnosis and treatment

Author: Julie, Di Lucca-Christment, Simon, Jacobelli, Ludivien, Gressier, Françoise, Plantier, Hélène, Laude, Flore, Rozenberg, Flore, Rosenberg, Jean-Pierre, Morini, Alexiane, Dallot, Marie-Françoise, Avril, and Nicolas, Dupin
Subjects: Adult, Male, Hepatitis C virus, Immunology, Human immunodeficiency virus (HIV), Organophosphonates, medicine.disease_cause, Antiviral Agents, Virus, Diagnosis, Differential, Myelopathy, Cytosine, immune system diseases, medicine, Immunology and Allergy, Humans, AIDS-Related Opportunistic Infections, business.industry, Papillomavirus Infections, virus diseases, Odds ratio, Middle Aged, medicine.disease, Virology, Thalidomide, Tumor Virus Infections, Infectious Diseases, Peripheral neuropathy, Treatment Outcome, Condylomata Acuminata, Coinfection, Carcinoma, Squamous Cell, Female, business, Cidofovir, Foscarnet
Abstract: HIV-individuals are at risk for human T-lymphotropic virus (HTLV) coinfection and neurological diseases. Little is known about the impact of HAART among coinfected patients. In this study, 47 out of 428 HIV individuals were coinfected with HTLV (10.9%). Coinfection was an independent variable associated with neurological outcome (odds ratio 8.73). Coinfection was associated with myelopathy [chi square (X2 ) U 93, P< 0.001], peripheral neuropathy (X2 U 6.5, P U 0.01), and hepatitis C virus infection (X2 U 36.5, P< 0.001). HAART did not appear to protect against neurological diseases and had no impact on HTLV proviral load.
Published: 2012

25. Valeur pronostique des anticorps anti-VP1 et anti-T du MCPyV dans une cohorte de patients avec carcinome de Merkel

Author: Nicolas Dupin, Serge Guyétant, Mahtab Samimi, A. Carlotti, L. Gouguet, Flore Rozenberg, Martine Avenel-Audran, C. Gardair, Nathalie Beneton, M.-F. Avril, L. Molet, E. Wierzbiecka Hainault, E. Maubec, Gérard Lorette, Anne Le Touze, Maxime Fleury, Eric Esteve, Pierre Coursaget, M. Baudin, François Aubin, and Hélène Laude
Subjects: viruses, Dermatology
Abstract: Introduction Le polyomavirus a cellules de Merkel (MCPyV) est l’agent etiologique de la majorite des carcinomes de Merkel (CCM). Les anticorps seriques diriges contre la proteine de capside VP1 du MCPyV (anti-VP1) sont detectes dans la majorite de la population, tandis que les anticorps diriges contre les oncoproteines du MCPyV (anti-T) sont specifiquement detectes chez les patients ayant un CCM. Nous avions anterieurement evalue dans une cohorte de patients avec CCM, la prevalence et les titres des anticorps anti-VP1 (J Clin Oncol, 2011) et des anticorps anti-T (JDP, 2011). L’objectif de cette etude etait d’evaluer la valeur pronostique (recidive et deces) des anticorps anti-MCPyV dans notre cohorte, ainsi que leur evolution au cours du suivi prolonge. Materiel et methodes Les anticorps anti-MCPyV etaient evalues dans le serum de 143 patients avec CCM par methode Elisa. L’antigene d’interet etait constitue par des pseudoparticules virales (anticorps anti-VP1) ou par une proteine recombinante constituee d’une sequence proteique commune aux oncoproteines virales couplee a la GST (anticorps anti-T). Observations NA. Resultats Les anticorps anti-T et anti-VP1 etaient detectes chez respectivement 45,2 % et 100 % des 84 patients ayant un prelevement serique disponible au diagnostic. Des titres eleves d’anticorps anti-VP1 (> 10 000) etaient associes de maniere independante et significative avec une diminution du risque de recidive ( p = 0,045) et de deces specifique lie au CCM ( p = 0,049), tandis que la detection d’anticorps anti-T au diagnostic n’etait pas associee au pronostic. Au cours du suivi, les anticorps anti-VP1 ne differaient pas entre les patients en remission et ceux en recidive et/ou progression. Au contraire, les anticorps anti-T etaient detectes de maniere plus frequente ( p = 0,005) et a des titres plus eleves ( p Discussion Nous avions montre en 2011 dans les premiers resultats que des titres eleves d’anticorps anti-VP1 etaient associes a une diminution du risque de recidive. Nous confirmons cet interet pronostique des anticorps anti-VP1 dans notre cohorte incrementee, et avec suivi prolonge. Nous montrons egalement, pour la premiere fois, que des titres eleves d’anticorps anti-VP1 sont associes de maniere independante et significative avec la survie specifique. Cependant, nous n’avons pas montre d’interet pronostique de la detection d’anticorps anti-T lors du diagnostic. Conclusion Les anticorps anti-VP1 eleves lors du diagnostic sont un marqueur pronostique favorable chez les patients ayant un CCM. La detection d’anticorps anti-T au-dela de 12 mois apres le diagnostic initial est associee a la recidive ou progression de la maladie.
Published: 2015

26. High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome

Author: Gérard Lorette, Eve Maubec, Agnès Carlotti, Annabel Maruani, Marie-Françoise Avril, Maxime Fleury, Raphaël Cazal, Serge Guyétant, Mauro Tognon, Flore Rozenberg, Françoise Arnold, Antoine Touzé, Emmanuelle Le Bidre, François Aubin, Pierre Coursaget, Hélène Laude, Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie, Hôpital Saint-Vincent de Paul, Laboratoire Analyse, Géométrie et Applications ( LAGA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut Galilée-Centre National de la Recherche Scientifique ( CNRS ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service de Dermatologie, Hôpital Cochin, AP-HP, Paris, Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]
Subjects: Pathology, MESH: Chi-Square Distribution, MESH: Lymphatic Metastasis, MESH: Polyomavirus, MESH : Aged, MESH : Prospective Studies, MESH: Risk Assessment, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Merkel cell carcinoma, 0302 clinical medicine, MESH: Up-Regulation, MESH : Neoplasm Staging, MESH : Up-Regulation, MESH: Capsid Proteins, 0303 health sciences, MESH: Middle Aged, Antibody titer, food and beverages, MESH : Lymphatic Metastasis, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Case-Control Studies, MESH : Polyomavirus, 3. Good health, Oncology, 030220 oncology & carcinogenesis, MESH: RNA, Viral, VIRUS, Antibody, MESH : Case-Control Studies, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Aged, 80 and over, MESH: Kaplan-Meier Estimate, MESH: Humans, MESH : Chi-Square Distribution, MESH : Humans, MESH: Adult, MESH : Proportional Hazards Models, medicine.disease, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, MESH: Female, SKIN, MESH: Antibodies, Viral, Cancer Research, MESH : Capsid Proteins, Merkel cell polyomavirus, Human skin, antibody, immune system, outcome, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, MESH: Risk Factors, MESH : Tumor Markers, Biological, INFECTION, EPIDEMIOLOGY, MESH : Female, MESH : Risk Assessment, MESH : Carcinoma, Merkel Cell, MESH: Aged, MESH : Prognosis, biology, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Neoplasm Staging, MESH : Adult, MESH : Risk Factors, MESH: Predictive Value of Tests, ETIOLOGY, MESH : Disease-Free Survival, MESH : Time Factors, circulatory and respiratory physiology, MESH : Antibodies, Viral, EXPRESSION, TISSUES, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Kaplan-Meier Estimate, medicine, MESH : RNA, Viral, MESH : France, 030304 developmental biology, Insect cell, business.industry, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH: Time Factors, Cancer, MESH: Carcinoma, Merkel Cell, biology.organism_classification, MESH: Male, MESH: Prospective Studies, MESH: France, Geometric mean titer, MCV, biology.protein, business
Abstract: Purpose A new human polyomavirus, Merkel cell polyomavirus (MCV), was identified in 2008 in tumor tissue of patients with Merkel cell carcinoma (MCC), a relatively rare human skin cancer. In this study, we investigated patients with MCC and controls for the presence of antibodies against MCV and their association with clinical characteristics. Patients and Methods Antibodies against MCV were investigated by enzyme-linked immunosorbent assay in 68 patients with MCC and 82 controls using VP1 virus-like particles produced in insect cells. Results Antibodies against MCV were detected in all patients with MCC and in 85% of controls. However, high antibody titers (> 10,000) were rarely observed in controls (7.3%) and they were detected in 64.7% of patients with MCC (P < .001) in contrast to the absence of VP1 expression in tumor samples. In addition, the geometric mean titer of anti-MCV in patients with MCC was around 14 times higher than that observed in MCV-positive controls (P < .001) and was not correlated with tumor viral load. High antibody titers were not found to be associated with any subject or tumor characteristics, but better progression-free survival was observed in patients with high antibody titers (hazard ratio, 4.6; 95% CI, 1.7 to 12.2; P = .002). Conclusion High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC. The findings also indicated that a better progression-free survival occurred in patients with high MCV antibody titers and suggested that there are at least two distinct etiologic causes of MCC.
Published: 2011

27. Epidermodysplasia verruciformis in human immunodeficiency virus-infected patients: a marker of human papillomavirus-related disorders not affected by antiretroviral therapy

Author: Flore Rozenberg, Jean-Pierre Morini, Marie-Françoise Avril, Jean Deleuze, S. Jacobelli, Isabelle Gorin, Hélène Laude, Agnès Carlotti, Nathalie Franck, and Nicolas Dupin
Subjects: Adult, Male, medicine.medical_specialty, Lymphoproliferative disorders, HIV Infections, Dermatology, Young Adult, Acquired immunodeficiency syndrome (AIDS), Immunopathology, Antiretroviral Therapy, Highly Active, medicine, Humans, Papillomaviridae, Skin, business.industry, Papillomavirus Infections, HPV infection, virus diseases, Papule, General Medicine, Pityriasis, Epidermodysplasia verruciformis, medicine.disease, Immunology, Epidermodysplasia Verruciformis, Female, Skin cancer, medicine.symptom, business
Abstract: Background: Skin eruptions resembling epidermodysplasia verruciformis (EV) are rarely observed in immunocompromised patients. We focused on the epidemiologic, clinical, virologic, and immunologic features of EV in human immunodeficiency virus (HIV)-positive patients. Observations:We studied 11 HIV-positive patients (6 men and 5 women) with clinical and histological features of EV observed at our department. The median age at HIV diagnosis was 27 years. At the onset of eruption, the median age was 40 years and the median CD4 T-cell countwas170/µL.Clinicalpresentationincludedflatwarts (n=11), pityriasis versicolor-like macules (n=5), and lichenoid papules (n=3) on sun-exposed skin. Detection and typing of cutaneous human papillomavirus (HPV) were carried out in 8 cases and always revealed -HPV infection, including oncogenic HPV-5 or 8 (n=6). Mucosal HPV-related diseases were present in 7 cases. Histories of skin cancer and lymphoproliferative disorder were recorded in 3 and 4 patients, respectively, including 2 fatal cases. Skin eruption was never improved by highlyactiveantiretroviraltherapy(HAART).In2cases, EV was associated with an immune reconstitution syndrome. The present series is the largest with a complete characterization.Areviewofsimilarcaseswascarriedout. Conclusion:Despite effective HAART, HIV-infected patients with EV require a prolonged and careful follow-uptodetectmucosalHPV-relateddiseases,lymphoproliferative disorders, and skin cancers.
Published: 2011

28. Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma

Author: Xavier Sastre-Garau, Martine Peter, Barbara Jonchère, Marie-Françoise Avril, Benoit Couturaud, Agnès Carlotti, Eve Maubec, Flore Rozenberg, Nicolas Dupin, Eduardo Marinho, and Hélène Laude
Subjects: Adult, Male, Skin Neoplasms, QH301-705.5, Immunoblotting, Immunology, Merkel cell polyomavirus, History, 18th Century, Polymorphism, Single Nucleotide, Oncology/Skin Cancers, Microbiology, Virology/Emerging Viral Diseases, Dermatology/Skin Cancers, including Melanoma and Lymphoma, Antigen, Virology, Genetics, Carcinoma, medicine, Humans, Biology (General), Molecular Biology, Aged, Neoplasm Staging, Proportional Hazards Models, Aged, 80 and over, Polyomavirus Infections, biology, Reverse Transcriptase Polymerase Chain Reaction, Merkel cell carcinoma, food and beverages, Middle Aged, RC581-607, medicine.disease, biology.organism_classification, Carcinoma, Merkel Cell, Tumor Virus Infections, DNA, Viral, Monoclonal, Leukocytes, Mononuclear, Female, Parasitology, Skin cancer, Immunologic diseases. Allergy, Polyomavirus, Viral load, Research Article, Virology/Viruses and Cancer
Abstract: Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associations between either MCPyV viral load in primary MCC or MCPyV DNAemia and survival. Results were interpreted with respect to the viral molecular signature in each compartment. Patients with MCC containing more than 1 viral genome copy per cell had a longer period in complete remission than patients with less than 1 copy per cell (34 vs 10 months, P = 0.037). Peripheral blood mononuclear cells (PBMC) contained MCPyV more frequently in patients sampled with disease than in patients in complete remission (60% vs 11%, P = 0.00083). Moreover, the detection of MCPyV in at least one PBMC sample during follow-up was associated with a shorter overall survival (P = 0.003). Sequencing of viral DNA from MCC and non MCC samples characterized common single nucleotide polymorphisms defining 8 patient specific strains. However, specific molecular signatures truncating MCPyV LT were observed in 8/12 MCC cases but not in respiratory and urinary samples from 15 patients. New integration sites were identified in 4 MCC cases. Finally, mutated-integrated forms of MCPyV were detected in PBMC of two patients with disseminated MCC disease, indicating circulation of metastatic cells. We conclude that MCPyV molecular features in primary MCC tumour and PBMC may help to predict the course of the disease., Author Summary Merkel cell polyomavirus (MCPyV) is a recently discovered virus highly associated with a rare skin cancer, Merkel cell carcinoma (MCC). The causal role of MCPyV in cancer is suggested by integration of viral sequences into the cell genome and by a specific molecular signature. We looked for and compared molecular species of MCPyV in tumour and non tumour samples of 33 MCC patients. We showed that a tumour viral load greater than 1 copy per cell was associated with a better outcome, and that detection of the virus in blood but not in urine correlated with a shorter overall survival. A tumour–specific molecular signature was found in the blood of two patients with metastatic disease, but did not occur in their respiratory nor urine samples. We propose that molecular analysis of MCPyV in tumour and blood be used as a biomarker of infection and cancer progression in MCC patients.
Published: 2010

29. Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis

Author: Martine Peter, Agnès Carlotti, Marie-Françoise Avril, Jérôme Couturier, Xavier Sastre-Garau, F. Boitier, Flore Rozenberg, Hélène Laude, Anna Almeida, Nicolas Dupin, and Benoit Couturaud
Subjects: Male, Skin Neoplasms, Virus Integration, Merkel cell polyomavirus, medicine.disease_cause, Virus Replication, Pathology and Forensic Medicine, Merkel Cells, medicine, Humans, Gene, In Situ Hybridization, Fluorescence, Aged, Aged, 80 and over, Comparative Genomic Hybridization, Polyomavirus Infections, biology, Merkel cell carcinoma, Middle Aged, biology.organism_classification, medicine.disease, Virology, Carcinoma, Merkel Cell, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Viral replication, DNA, Viral, RNA, Viral, Female, Merkel cell, Carcinogenesis, Polyomavirus, circulatory and respiratory physiology, Comparative genomic hybridization
Abstract: Merkel cell carcinoma (MCC), a skin tumour with neuroendocrine features, was recently found to be associated with a new type of human polyomavirus, called Merkel cell virus (MCV). We investigated the specificity of this association as well as a causal role of MCV in oncogenesis. DNA and RNA from ten cases of MCC were analysed using PCR and RT-PCR. DNA from 1241 specimens of a wide range of human tumours was also analysed. The DIPS technique was used to identify the integration locus of viral DNA sequences. Array CGH was performed to analyse structural alterations of the cell genome. MCV DNA sequences were found in all ten cases of MCC and in none of the 1241 specimens of other tumour types. Clonal integration of MCV into the host genome was seen in all MCC cases and was checked by FISH in one case. A recurrent pattern of conserved viral sequences which encompassed the replication origin, the small tumour (ST), and the 5' part of the large tumour (LT) antigen DNA sequences was observed. Both ST and LT viral sequences were found to be significantly expressed in all MCCs. Neither recurrent site of integration nor alteration of cellular genes located near the viral sequences was observed. The tight association of MCV with MCC, the clonal pattern of MCV integration, and the expression of the viral oncoproteins strongly support a causative role for MCV in the tumour process. This information will help the development of novel approaches for the assessment and therapy of MCC and biologically related tumours.
Published: 2009

30. Stepwise development of MAIT cells in mouse and human

Author: Claire Soudais, Ivan C. Moura, Stéphane Cherif, Hélène Laude, Emmanuel Martin, Lucia Guerri, Cécile Toly, Livine Duban, Anne Devys, Florence Tilloy, Sylvain Latour, Virginie Premel, Gabriella Vera, Olivier Lantz, Emmanuel Treiner, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm U925, équipe avenir, Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Nantes], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from INSERM, Action incitative (ACI) 'physiologie integrative,' Agence Nationale pour la Recherche (ANR), and Section Médicale de l'Institut Curie. The development of the 3C10 antibody was funded in part by Innate-Pharma (Marseille, France). OL is supported by la Ligue Contre le Cancer as an 'équipe labellisée.', Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Immunité et cancer (U932), and Autard, Delphine
Subjects: Adoptive cell transfer, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Kruppel-Like Transcription Factors, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, Mice, 0302 clinical medicine, MESH : Child, T-Lymphocyte Subsets, MESH: Child, Cytotoxic T cell, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Biology (General), Child, Mice, Knockout, 0303 health sciences, B-Lymphocytes, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH : Immunity, Mucosal, General Neuroscience, Natural killer T cell, Fetal Blood, MESH : Mice, Transgenic, Cell biology, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH : Histocompatibility Antigens Class I, MESH: Kruppel-Like Transcription Factors, Antibody, General Agricultural and Biological Sciences, Research Article, Genetically modified mouse, MESH: Mice, Transgenic, QH301-705.5, Immunology, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Thymus Gland, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, MESH : B-Lymphocytes, Minor Histocompatibility Antigens, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Mice, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, MESH : Thymus Gland, MESH: Fetal Blood, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunity, Mucosal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : T-Lymphocytes, MESH : Fetal Blood, MESH: Humans, General Immunology and Microbiology, T-cell receptor, Histocompatibility Antigens Class I, MESH : Humans, MESH: Thymus Gland, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Gastrointestinal Tract, MESH: T-Lymphocytes, MESH: Natural Killer T-Cells, MESH: Immunity, Mucosal, biology.protein, Natural Killer T-Cells, MESH : Mice, Knockout, MESH: Gastrointestinal Tract, MESH : Animals, MESH : Gastrointestinal Tract, 030215 immunology
Abstract: Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)α (iTCRα) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanVα7.2 antibody and MAIT cell-specific iTCRα and TCRβ transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRα and TCRβ transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%–4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and γδ T cells., Author Summary White blood cells, or lymphocytes, play an important role in defending the body from infection and disease. T lymphocytes come in many varieties with diverse functions. Mucosal-associated invariant T (MAIT) cells constitute a subset of unconventional T lymphocytes, characterized by their invariant T cell receptor (TCR)α chain and their requirement for the nonpolymorphic class Ib (MHC) molecule, MR1. MAIT cells are extremely abundant in human blood and mucosae. Contrary to mainstream T cells, their development requires B cells and commensal microbial flora. To shed light on the little-understood MAIT cells, we used new tools, including an antibody that we recently developed to detect human MAIT cells, and we were able to show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. We show that thymic selection is MR1 dependent but requires neither B cells nor the commensal flora, which are both necessary for the expansion in the periphery. In contrast with the other evolutionarily conserved invariant subset, the natural killer T (NKT) cells, we found that MAIT cells exit the thymus as “naïve” cells before becoming antigen-experienced memory cells and expanding in number to represent a significant 1%–4% of peripheral T cells in human blood. In mice, we found that MAIT cells remain naïve and do not expand substantially. We conclude that MAIT cell development follows a unique scheme, where, unlike NKT cells, MAIT cell selection and expansion are uncoupled events that are mediated by distinct cell types in different compartments., Mucosal-associated invariant T cells, the most abundant invariant T cell subset in humans, arise via a distinct developmental pathway that represents a hybrid of that seen for NKT and γδ T cells, two other unconventional T cell subsets.
Published: 2009

31. Anticorps dirigés contre l’antigène T du polyomavirus à cellules de Merkel chez les patients avec un carcinome de Merkel

Author: Mauro Tognon, Serge Guyétant, Flore Rozenberg, Mahtab Samimi, Ludovic Martin, A. Carlotti, François Aubin, Gérard Lorette, M.-F. Avril, E. Le Bidre, Hélène Laude, M. Avenel Audran, E. Maubec, Maxime Fleury, Anne Le Touze, and Pierre Coursaget
Subjects: Dermatology
Published: 2011

32. Fulminant Type 1 Diabetes in the Course of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome

Author: Hélène Laude, Danièle Dubois-Laforgue, José Timsit, and Laurence Moachon
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, Abdominal pain, business.industry, Endocrinology, Diabetes and Metabolism, Fulminant, medicine.disease, Dermatology, Tachypnea, Rash, Polyuria, Anesthesia, Internal Medicine, Vomiting, medicine, Eosinophilia, Bronchitis, Online Letters: Observations, medicine.symptom, business
Abstract: DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome is a life-threatening drug reaction. Its management relies on discontinuation of the culprit drug and treatment with corticosteroids (1). A 68-year-old Filipino woman was admitted for ketoacidosis (DKA), revealing diabetes. Four months before admission, she had been treated for bronchitis with erythromycin, then moxifloxacin. A transient skin rash occurred. Six days before admission, she was treated with amoxicillin/clavulanic acid for recurrence of bronchitis, and fever and a pruritic skin rash occurred. Four days later, the patient was admitted for drowsiness, tachypnea, and vomiting. She reported no abdominal pain, no weight loss (BMI 20.3 kg/m2), and no polyuria. Physical examination disclosed facial erythema, palpebral edema, conjunctivitis, generalized maculopapular skin rash, cheilitis, and diffuse lymph node …
Published: 2013

33. Acknowledgement to Referees for Dermatology 2010

Author: Eckart Haneke, Rudolf Happle, Zoe Daniil, Daniele Torchia, M. Lahfa, Hélène Laude, Julia Hanfland, Foteini Malli, Shinichi Tobisawa, F. Rongioletti, A.M. Skaria, B.A. Aigner, Konstantinos I. Gourgoulianis, Thomas Bieber, Akemi Ishida-Yamamoto, J. Mazereeuw-Hautier, B. Pasini, Ichiro Takahashi, Suzanne Hauffe, Tetsuo Shiohara, Noriko Aota Sato, N. Cardot-Leccia, L. Toutous-Trellu, Hajime Iizuka, Amir Gal-Oz, Natalia Garcia-Aranda, Diamant Thaçi, F.M. Hajjaj, M.K.A. Basra, Takashi Shibuya, Miquel Vilardell-Tarrés, J. Boyle, J.P. Tolland, Severin Läuchli, C. Paul, P. Mandich, Nadège Wallet-Faber, M. Kostaki, Stephan Koehne-Voss, H. Montaudié, J. Kohlhase, V. Piguet, K.E. McKenna, Marie-Françoise Avril, Francesc Miró-Mur, Dieter Mayer, A. Volz, A.Y. Finlay, Natalie Ortega-Zilic, Satz Mengensatzproduktion, Masaru Honma, Carine Houriet, X.C. Pham, Agnès Carlotti, C. Bulai Livideanu, Shmuel Kivity, J. Ring, B.V. Stimec, Victor Garcia-Gimenez, L. Bruckner-Tuderman, Michael Swartzon, S.G. Plötz, Druck Reinhardt Druck Basel, B. Ferrando, Nicolas Dupin, Ori Rogowski, V. Hall, N. Sebbag, U. Darsow, D. Salomon, Lars E. French, J.P. Lacour, Shin Iinuma, Johan Chanal, T. Passeron, G. Kaya, Katrin Baumann Conzett, J.S. Elborn, Kirstin Sippel, M.S. Salek, P. Itin, B. Burger, Roland Kaufmann, J.H.D. Fasel, Nedzmidin Pelivani, M. Becker, M. Grosber, V. Fausti, Jürg Hafner, Thomas Hunziker, Felix Waldmeier, C. Has, Irene Planells-Romeu, Shigetsuna Komatsu, Clarissa Huber, A. Parodi, Yoko Kano, Jaume Alijotas-Reig, and Luca Borradori
Subjects: Medical education, Acknowledgement, Dermatology, Psychology
Published: 2010

34. Olfactory outcomes in Zika virus-associated Guillain-Barré syndrome

Author: Françoise, Lazarini, Annie, Lannuzel, André, Cabié, Vincent, Michel, Yoann, Madec, Hugo, Chaumont, Isabelle, Calmont, Mathilde, Favrat, Xavier, Montagutelli, Emmanuel, Roze, Pierre-Marie, Lledo, Marie-Noëlle, Ungeheuer, Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pointe-à-Pitre/Abymes [Guadeloupe], CHU de la Martinique [Fort de France], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), 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)-Université Paris Cité (UPCité)-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), Génétique de la souris - Mouse Genetics, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This study was funded and sponsored by CHU of Martinique (Zikasmell ancillary study of the CARBO cohort) and supported by the French Ministry of Health (Exceptional Support for Research and Innovation and Clinical Research Hospital Program, PHRC 2009 NCT01099852), REACTing (INSERM) and Institut Pasteur (GPF 2015 Microbes & Brain 'INFECSMELL')., Zikasmell working group: Françoise Lazarini, Annie Lannuzel, André Cabié, Isabelle Calmont, Sylvie Abel, Ornella Cabras, Athéna Marquise, Mathilde Pircher, Aïssatou Signate, Christelle Celeste, Hugo Chaumont, Angela Lackmy, Guillaume Lepage, Quentin Lobjois, Aimée Petit, Benoît Tressières, Natacha Teissier, Emmanuel Roze, Tan-Phuc Buivan, Laurine Conquet, Hélène Laude, Pierre-Marie Lledo, Yoann Madec, Estelle Mottez, Fabien Taieb, Marie-Noëlle Ungeheuer., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Etablissement français du don du sang [Montpellier], Université Paris Cité (UPC)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Paris Cité (UPC)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), Institut Pasteur [Paris]-Université Paris Cité (UPC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: olfactory threshold, Zika Virus Infection, hyposmia, COVID-19, Zika Virus, Guillain-Barre Syndrome, Olfaction, Smell, Mice, Guillain Barré Syndrome, Zika, Neurology, Animals, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical)
Abstract: International audience; Background: Zika Virus (ZIKV) infection has been associated with Guillain-Barré Syndrome (GBS). Yet, little is known about the consequence of ZIKV infection on olfaction in humans. Methods: Just right before the COVID-19 outbreak, we prospectively investigated the olfacto-ry capacities of 19 patients with ZIKV-associated GBS from the French West Indies and com-pared them to 9 controls from the same population, with a GBS of similar severity but inde-pendent of Zika infection. To provide further evidence that ZIKV infection induces smell altera-tion, we investigated the consequences of ZIKV infection on olfactory abilities using a mouse model.Results: Patients with GBS-Zika+ had a poorer olfactory function than GBS-non-Zika, even one to two years after the acute phase. The proportion of patients with hyposmia was signifi-cantly higher in GBS-Zika+ than in GBS-non-Zika group (68.4% versus 22.2%, P=0.042). These deficits were characterized by lower threshold and identification scores and were inde-pendent from GBS severity. Additionally, ZIKV infection was found to impair olfaction in immu-nodeficient mice infected with ZIKV. High viral load was observed in their olfactory system and downstream brain structures. ZIKV promoted both cellular damages in the olfactory neuroepi-thelium and protracted inflammation of the olfactory bulb, likely accounting for smell alteration. Conclusions: Patients with ZIKV-related GBS had a poorer long-term olfactory function than patients with GBS-non-Zika and ZIKV-infected mice are hyposmic. These observations sug-gest that ZIKV belongs to the list of viruses affecting the olfactory system. Clinical evaluation of the olfactory system should be considered for ZIKV-infected patients.
Published: 2022

35. Dengue virus NS1 protein conveys pro‐inflammatory signals by docking onto high‐density lipoproteins

Author: Souheyla Benfrid, Kyu‐Ho Park, Mariano Dellarole, James E Voss, Carole Tamietti, Gérard Pehau‐Arnaudet, Bertrand Raynal, Sébastien Brûlé, Patrick England, Xiaokang Zhang, Anastassia Mikhailova, Milena Hasan, Marie‐Noëlle Ungeheuer, Stéphane Petres, Scott B Biering, Eva Harris, Anavaj Sakuntabhai, Philippe Buchy, Veasna Duong, Philippe Dussart, Fasséli Coulibaly, François Bontems, Félix A Rey, Marie Flamand, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes, Sorbonne Paris Cité, Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), University of California [Berkeley] (UC Berkeley), University of California (UC), Génétique du Développement humain - Human developmental genetics, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Monash University [Clayton], Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), This study benefited from the financial support of the Institut Pasteur ACIP-27-16 (P.D., V.D., M.F.), the Institut Pasteur Dengue Task Force (to MF), the Institut Pasteur INNOV-44-19 (M.F), the National Natural Science Foundation of China 31600606 (X.Z.), the National Key R&D Program of China 2016YFA0501100 (X.Z.), Guangdong Provincial Key Laboratory of Brain Connectome and Behavior 2017B030301017 (X.Z.), CAS Key Laboratory of Brain Connectome and Manipulation 2019DP173024 (X.Z.), the NIAID/NIH R01 AI24493 (E.H.) and R21 AI146464 (E.H.), ANR Equipex CACSICE ANR-11-EQPX-0008 (G.P.-A.)., The authors gratefully acknowledge the staff of the Kampong Cham Referral Hospital, the patients and parents who participated in the study, and the Arbovirus Team in the Virology Unit at the Institut Pasteur du Cambodge who contributed to this study. We acknowledge the participation of the ICAReB facility in setting up the recruitment of donors and the acquisition of blood samples, in particular Gloria Morizot, Bianca Liliana Perlaza, Sophie Chaouche, Linda Sangari, Céline Chapel, Philippe Esterre and Hélène Laude. We are most grateful to Christine Girard-Blanc and Evelyne Dufour for their contribution in producing and purifying the recombinant DENV NS1 protein, to Béatrice Poirier-Beaudouin and Cartini Mardi for their help in setting up the cytokine quantification assay, to Arvind Sharma for providing purified anti-E MAbs, to Mathilde Ban for preparing Fab-bound NS1-HDL complexes and to Xavier Montagutelli and Etienne Simon-Lorière for testing an in vivo protection assay. We thank M. Nilges and the Equipex CACSICE for providing the Falcon II direct detector and David Veesler for his help in acquiring the first electron microscopy images of the bovine NS1-HDL complex. Finally, we thank Sébastien Quesney, Alexandre Pachot and Karine Kaiser for their support. The synopsis figure was created with BioRender.com., and ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011)
Subjects: Arbovirus, lipoprotein particle, viruses, accessory protein, virus diseases, Dengue Virus, Viral Nonstructural Proteins, biochemical phenomena, metabolism, and nutrition, Biochemistry, virulence factor, Dengue, molecular pathogenesis, Phagocytosis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, Molecular Biology, hemorrhagic fever
Abstract: International audience; The dengue virus nonstructural protein 1 (NS1) is a secreted virulence factor that modulates complement, activates immune cells and alters endothelial barriers. The molecular basis of these events remains incompletely understood. Here we describe a functional high affinity complex formed between NS1 and human high-density lipoproteins (HDL). Collapse of the soluble NS1 hexamer upon binding to the lipoprotein particle leads to the anchoring of amphipathic NS1 dimeric subunits into the HDL outer layer. The stable complex can be visualized by electron microscopy as a spherical HDL with rod-shaped NS1 dimers protruding from the surface. We further show that the assembly of NS1-HDL complexes triggers the production of pro-inflammatory cytokines in human primary macrophages while NS1 or HDL alone do not. Finally, we detect NS1 in complex with HDL and low-density lipoprotein (LDL) particles in the plasma of hospitalized dengue patients and observe NS1-apolipoprotein E-positive complexes accumulating overtime. The functional reprogramming of endogenous lipoprotein particles by NS1 as a means to exacerbate systemic inflammation during viral infection provides a new paradigm in dengue pathogenesis.
Published: 2022

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35 results on '"Hélène Laude"'

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35. Dengue virus NS1 protein conveys pro‐inflammatory signals by docking onto high‐density lipoproteins

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