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1. Multifaceted contributions of Dicer2 to arbovirus transmission by Aedes aegypti

Author

Sarah Hélène Merkling, Anna Beth Crist, Annabelle Henrion-Lacritick, Lionel Frangeul, Elodie Couderc, Valérie Gausson, Hervé Blanc, Alexander Bergman, Artem Baidaliuk, Ottavia Romoli, Maria-Carla Saleh, and Louis Lambrechts

Subjects
CP: Immunology, CP: Microbiology, Biology (General), QH301-705.5
Abstract

Summary: Arthropod-borne viruses (arboviruses) transmitted by Aedes aegypti mosquitoes are an increasing threat to global health. The small interfering RNA (siRNA) pathway is considered the main antiviral immune pathway of insects, but its effective impact on arbovirus transmission is surprisingly poorly understood. Here, we use CRISPR-Cas9-mediated gene editing in vivo to mutate Dicer2, a gene encoding the RNA sensor and key component of the siRNA pathway. The loss of Dicer2 enhances early viral replication and systemic viral dissemination of four medically significant arboviruses (chikungunya, Mayaro, dengue, and Zika viruses) representing two viral families. However, Dicer2 mutants and wild-type mosquitoes display overall similar levels of vector competence. In addition, Dicer2 mutants undergo significant virus-induced mortality during infection with chikungunya virus. Together, our results define a multifaceted role for Dicer2 in the transmission of arboviruses by Ae. aegypti mosquitoes and pave the way for further mechanistic investigations.

Published
2023
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2. Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen

Author

Alice Mac Kain, Ghizlane Maarifi, Sophie-Marie Aicher, Nathalie Arhel, Artem Baidaliuk, Sandie Munier, Flora Donati, Thomas Vallet, Quang Dinh Tran, Alexandra Hardy, Maxime Chazal, Françoise Porrot, Molly OhAinle, Jared Carlson-Stevermer, Jennifer Oki, Kevin Holden, Gert Zimmer, Etienne Simon-Lorière, Timothée Bruel, Olivier Schwartz, Sylvie van der Werf, Nolwenn Jouvenet, Sébastien Nisole, Marco Vignuzzi, and Ferdinand Roesch

Subjects
Science
Abstract

Here, Mac Kain and Maarifi et al. perform a functional CRISPR/Cas9 screen to identify SARS-CoV-2 restriction factors in A549 cells. They identify DAXX, a scaffold protein of nuclear bodies with diverse functions, that has anti-viral activity post SARS-CoV-2 entry, while SARS-CoV-2 has evolved a mechanism to counteract its action via PLpro-mediated proteasomal degradation.

Published
2022
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3. A novel SARS-CoV-2 related coronavirus in bats from Cambodia

Author

Deborah Delaune, Vibol Hul, Erik A. Karlsson, Alexandre Hassanin, Tey Putita Ou, Artem Baidaliuk, Fabiana Gámbaro, Matthieu Prot, Vuong Tan Tu, Sokha Chea, Lucy Keatts, Jonna Mazet, Christine K. Johnson, Philippe Buchy, Philippe Dussart, Tracey Goldstein, Etienne Simon-Lorière, and Veasna Duong

Subjects
Science
Abstract

In this study, Delaune et al., isolate and characterise a SARS-CoV-2-related coronavirus from two bats sampled in Cambodia. Their findings suggest that the geographic distribution of SARS-CoV-2-related viruses is wider than previously reported.

Published
2021
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4. Recent African strains of Zika virus display higher transmissibility and fetal pathogenicity than Asian strains

Author

Fabien Aubry, Sofie Jacobs, Maïlis Darmuzey, Sebastian Lequime, Leen Delang, Albin Fontaine, Natapong Jupatanakul, Elliott F. Miot, Stéphanie Dabo, Caroline Manet, Xavier Montagutelli, Artem Baidaliuk, Fabiana Gámbaro, Etienne Simon-Lorière, Maxime Gilsoul, Claudia M. Romero-Vivas, Van-Mai Cao-Lormeau, Richard G. Jarman, Cheikh T. Diagne, Oumar Faye, Ousmane Faye, Amadou A. Sall, Johan Neyts, Laurent Nguyen, Suzanne J. F. Kaptein, and Louis Lambrechts

Subjects
Science
Abstract

Here, the authors compare seven low passage Zika virus (ZIKV) strains representing the recently circulating viral genetic diversity of African and Asian strains and find that African ZIKV strains have higher transmissibility in mosquitoes and higher lethality in both adult and fetal mice.

Published
2021
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5. Fusogenicity and neutralization sensitivity of the SARS-CoV-2 Delta sublineage AY.4.2

Author

Nell Saunders, Delphine Planas, William H. Bolland, Christophe Rodriguez, Slim Fourati, Julian Buchrieser, Cyril Planchais, Matthieu Prot, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, David Veyer, Hélène Péré, Nicolas Robillard, Madelina Saliba, Artem Baidaliuk, Aymeric Seve, Laurent Hocqueloux, Thierry Prazuck, Felix A. Rey, Hugo Mouquet, Etienne Simon-Lorière, Timothée Bruel, Jean-Michel Pawlotsky, and Olivier Schwartz

Subjects
SARS-CoV-2, Delta, AY.4.2, Vaccines, Fusogenicity, Neutralization, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: SARS-CoV-2 lineages are continuously evolving. As of December 2021, the AY.4.2 Delta sub-lineage represented 20 % of sequenced strains in the UK and had been detected in dozens of countries. It has since then been supplanted by Omicron. The AY.4.2 spike displays three additional mutations (T95I, Y145H and A222V) in the N-terminal domain when compared to the original Delta variant (B.1.617.2) and remains poorly characterized. Methods: We compared the Delta and the AY.4.2 spikes, by assessing their binding to antibodies and ACE2 and their fusogenicity. We studied the sensitivity of an authentic AY.4.2 viral isolate to neutralizing antibodies. Findings: The AY.4.2 spike exhibited similar binding to all the antibodies and sera tested, and similar fusogenicity and binding to ACE2 than the ancestral Delta spike. The AY.4.2 virus was slightly less sensitive than Delta to neutralization by a panel of monoclonal antibodies; noticeably, the anti-RBD Imdevimab showed incomplete neutralization. Sensitivity of AY.4.2 to sera from vaccinated individuals was reduced by 1.3 to 3-fold, when compared to Delta. Interpretation: Our results suggest that mutations in the NTD remotely impair the efficacy of anti-RBD antibodies. The spread of AY.4.2 was not due to major changes in spike fusogenicity or ACE2 binding, but more likely to a partially reduced neutralization sensitivity. Funding: The work was funded by Institut Pasteur, Fondation pour la Recherche Médicale, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute, Labex IBEID, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR.

Published
2022
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6. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

Author

Najiby Kassis-Chikhani, Samira Fafi-Kremer, Olivier Schwartz, Laurent Bélec, Matthieu Prot, Cyril Planchais, Timothée Bruel, Laura Courtellemont, Florence Guivel-Benhassine, Artem Baidaliuk, Isabelle Staropoli, Julien Le Guen, Etienne Simon-Loriere, Laurent Hocqueloux, Delphine Planas, David Veyer, Pierre Gantner, Maaran Michael Rajah, Aurélie Velay, Thierry Prazuck, Dhiaeddine Edriss, Félix A. Rey, Françoise Porrot, Hélène Péré, Floriane Gallais, Aymeric Sève, Nicolas Robillard, Julien Puech, Hugo Mouquet, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Virologie Structurale - Structural Virology, The Opera system was co-funded by the Institut Pasteur and the Région Île de France (DIM1Health). Work in the O.S. laboratory is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and the Région Île-de-France program DIM1-Health. D.P. is supported by the Vaccine Research Institute. The H.M. laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, REACTing, EU (RECOVER) and Fondation de France (00106077) grants. The S.F.K. laboratory is funded by Strasbourg University Hospitals (SeroCoV-HUS, PRI 7782), the Programme Hospitalier de Recherche Clinique (PHRC N 2017–HUS no. 6997), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d’Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX) and the Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). The E.S.-L. laboratory is funded by the Institut Pasteur and the French Government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID)., We thank N. Casartelli for critical reading of the manuscript, P. Guardado Calvo for discussion, the individuals who participated in the study, members of the Virus and Immunity Unit for discussions and help, N. Aulner and the UTechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis, and the DRCI, CIC, Médecine du Travail and Pôle de Biologie teams (CHU de Strasbourg) for the management of the Strasbourg cohort and serology testing., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), and Université Paris Cité (UPC)

Subjects
Male, Delta, COVID-19 Vaccines, medicine.drug_class, India, Alpha (ethology), Biology, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Monoclonal antibody, Neutralization, Epitope, Epitopes, Immune system, Neutralization Tests, medicine, Humans, Immune Evasion, Multidisciplinary, COVID-19, Convalescence, Middle Aged, Antibodies, Neutralizing, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Spike Glycoprotein, Coronavirus, Monoclonal, biology.protein, France, Antibody
Abstract

The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1–5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2—also termed the Delta variant—is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein. The SARS-CoV-2 Delta variant partially evades neutralization by several monoclonal antibodies and by sera from individuals who have had COVID-19, but two doses of anti-COVID-19 vaccines still generate a strong neutralizing response.

Published
2021

7. Tecovirimat is highly efficient on the Monkeypox virus lineage responsible for the international 2022 outbreak

Author

Gaëlle Frenois-Veyrat, Franck Gallardo, Olivier Gorgé, Elie Marcheteau, Olivier Ferraris, Artem Baidaliuk, Anne-Laure Favier, Cécile Enfroy, Xavier Holy, Jérémy Lourenco, Rhéa Khoury, Flora Nolent, Douglas W. Grosenbach, Dennis Hruby, Audrey Ferrier, Frédéric Iseni, Etienne Simon-Loriere, Jean-Nicolas Tournier, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), NeoVirTech (FRANCE), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Maison médicale Chemin vert [Paris], Cerballiance, SIGA Technologies [Corvallis, OR], École du Val de Grâce (EVDG), Service de Santé des Armées, E.S.-L. acknowledges funding from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005), from the PICREID program and from the Labex IBEID (ANR-10-LABX-62-IBEID). O.F., A.F.-R. and J.-N.T. acknowledge the support from Santé Publique France for the CNR-LE orthopoxvirus. F.I. acknowledges funding from the Direction Généralede l’Armement (DGA) (Biomedef PDH-2-NRBC-4-B-4111). F.G acknowledges funding from the Agence Innovation Défense (AID) (RAPID DENALPOVIR 192906106), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)

Subjects
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract

The ongoing monkeypox virus (MPXV) outbreak is the largest ever recorded outside of Africa. Genomic analysis revealed a divergent phylogenetic lineage within clade 3, and atypical clinical presentations have been noted. We report the sequencing and isolation of the virus from the first clinical case diagnosed in France in May 2022. We tested thein vitroeffect of tecovirimat (ST-246), a FDA approved drug, against this novel strain, showing efficacy at the nanomolar range. In comparison, cidofovir showed activity at micromolar concentrations. These results and the safety profile of tecovirimat strongly support its use in clinical care of severe forms for the 2022 MPXV outbreak.

Published
2022

8. Tecovirimat is effective against human monkeypox virus in vitro at nanomolar concentrations

Author

Gaëlle Frenois-Veyrat, Franck Gallardo, Olivier Gorgé, Elie Marcheteau, Olivier Ferraris, Artem Baidaliuk, Anne-Laure Favier, Cécile Enfroy, Xavier Holy, Jérémy Lourenco, Rhéa Khoury, Flora Nolent, Douglas W. Grosenbach, Dennis E. Hruby, Audrey Ferrier, Frédéric Iseni, Etienne Simon-Loriere, and Jean-Nicolas Tournier

Subjects
Microbiology (medical), Immunology, Benzamides, Genetics, Humans, Cell Biology, Monkeypox, Monkeypox virus, Isoindoles, Applied Microbiology and Biotechnology, Microbiology, United States
Abstract

The ongoing monkeypox virus (MPXV) outbreak is the largest ever recorded outside of Africa. We isolated and sequenced a virus from the first clinical MPXV case diagnosed in France (May 2022). We report that tecovirimat (ST-246), a US Food and Drug Administration approved drug, is efficacious against this isolate in vitro at nanomolar concentrations, whereas cidofovir is only effective at micromolar concentrations. Our results support the use of tecovirimat in ongoing human clinical trials.

Published
2022

9. Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies

Author

Timothée Bruel, Jérôme Hadjadj, Piet Maes, Delphine Planas, Aymeric Seve, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, William-Henry Bolland, Yann Nguyen, Marion Casadevall, Caroline Charre, Hélène Péré, David Veyer, Matthieu Prot, Artem Baidaliuk, Lize Cuypers, Cyril Planchais, Hugo Mouquet, Guy Baele, Luc Mouthon, Laurent Hocqueloux, Etienne Simon-Loriere, Emmanuel André, Benjamin Terrier, Thierry Prazuck, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Cité (UPCité), 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), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Work in the O.S. lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR Coronamito and IDISCOVR. Work in the UPBI facility is funded by grant ANR-10-INSB-04-01 and the Région Ȋle-de-France program DIM1Health. D.P. is supported by the Vaccine Research Institute. G.B. acknowledges support from the Internal Funds KU Leuven under grant agreement C14/18/094 and the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G0E1420N and G098321N). P.M. acknowledges support from a COVID-19 research grant of ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation Flanders (grant G0H4420N). P.M. acknowledges support of a COVID-19 research grant from ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation Flanders (grant G0H4420N) and ‘Internal Funds KU Leuven’ (grant 3M170314). E.S.L. acknowledges funding from the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005)., We thank the European Health Emergency Preparedness and Response Authority (HERA) for supporting the work being done at Institut Pasteur and UK Leuven. We thank J. Buchrieser, J. Puech and F. Gambaro for their help with the sequencing data analysis. We thank the patients who participated to this study. We thank Y. Yazdanpanah, members of the Virus and Immunity Unit and other teams for discussions and help, N. Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis. The Opera system was co-funded by Institut Pasteur and the Région Ȋle-de-France (DIM1Health). We thank the KU Leuven University authorities and J. Arnout, B. Lambrecht, C. Van Geet and L. Sels for their support. We thank F. Peira, V. Legros and L. Courtellemont for their help with the cohorts. UZ Leuven, as national reference center for respiratory pathogens, is supported by Sciensano, which is gratefully acknowledged., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE)

Subjects
Membrane Glycoproteins, SARS-CoV-2, Antibodies, Monoclonal, General Medicine, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology, COVID-19 Drug Treatment, Viral Envelope Proteins, Neutralization Tests, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans
Abstract

International audience; The severe acute respiratory syndrome coronavirus 2 Omicron BA.1 sublineage has been supplanted in many countries by the BA.2 sublineage. BA.2 differs from BA.1 by about 21 mutations in its spike. In this study, we first compared the sensitivity of BA.1 and BA.2 to neutralization by nine therapeutic monoclonal antibodies (mAbs). In contrast to BA.1, BA.2 was sensitive to cilgavimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab. We then analyzed sera from 29 immunocompromised individuals up to 1 month after administration of Ronapreve (casirivimab and imdevimab) and/or Evusheld (cilgavimab and tixagevimab) antibody cocktails. All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (nine-fold). We further report four breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve and, to a lesser extent, that of Evusheld is reduced in patients' sera.

Published
2022

10. Seroneutralization of Omicron BA.1 and BA.2 in patients receiving anti-SARS-CoV-2 monoclonal antibodies

Author

Timothée Bruel, Jérôme Hadjadj, Piet Maes, Delphine Planas, Aymeric Seve, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, William-Henry Bolland, Yann Nguyen, Marion Casadevall, Caroline Charre, Hélène Péré, David Veyer, Matthieu Prot, Artem Baidaliuk, Lize Cuypers, Cyril Planchais, Hugo Mouquet, Guy Baele, Luc Mouthon, Laurent Hocqueloux, Etienne Simon-Loriere, Emmanuel André, Benjamin Terrier, Thierry Prazuck, and Olivier Schwartz

Abstract

The SARS-CoV-2 Omicron BA.1 variant has been supplanted in many countries by the BA.2 sub-lineage. BA.2 differs from BA.1 by about 21 mutations in its spike. Human anti-spike monoclonal antibodies (mAbs) are used for prevention or treatment of COVID-19. However, the capacity of therapeutic mAbs to neutralize BA.1 and BA.2 remains poorly characterized. Here, we first compared the sensitivity of BA.1 and BA.2 to neutralization by 9 therapeutic mAbs. In contrast to BA.1, BA.2 was sensitive to Cilgavimab, partly inhibited by Imdevimab and resistant to Adintrevimab and Sotrovimab. Two combinations of mAbs, Ronapreve (Casirivimab + Imdevimab) and Evusheld (Cilgavimab + Tixagevimab), are indicated as a pre-exposure prophylaxis in immunocompromised persons at risk of severe disease. We analyzed sera from 29 such individuals, up to one month after administration of Ronapreve and/or Evusheld. After treatment, all individuals displayed elevated antibody levels in their sera and neutralized Delta with high titers. Ronapreve recipients did not neutralize BA.1 and weakly impaired BA.2. With Evusheld, neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 patients, respectively. As compared to Delta, titers were more severely decreased against BA.1 (344-fold) than BA.2 (9-fold). We further report 4 breakthrough Omicron infections among the 29 participants. Therefore, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron activity of Ronapreve, and to a lesser extent that of Evusheld, is reduced in patients’ sera, a phenomenon associated with decreased clinical efficacy.

Published
2022

11. Identification of DAXX As A Restriction Factor Of SARS-CoV-2 Through A CRISPR/Cas9 Screen

Author

Alice Mac Kain, Françoise Porrot, Ferdinand Roesch, Molly OhAinle, Etienne Simon-Loriere, Nolwenn Jouvenet, Artem Baidaliuk, Kevin Holden, Nathalie J. Arhel, Alexandra Hardy, Quang Dinh Tran, Olivier Schwartz, Marco Vignuzzi, Sébastien Nisole, Thomas Vallet, Sophie-Marie Aicher, Jennifer Oki, Timothée Bruel, Maxime Chazal, Jared Carlson-Stevermer, Ghizlane Maarifi, and Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Cas9, viruses, [SDV]Life Sciences [q-bio], fungi, DNA replication, virus diseases, Biology, Sumoylation Pathway, Virology, Virus, 3. Good health, body regions, 03 medical and health sciences, 0302 clinical medicine, Death-associated protein 6, Viral replication, Interferon, medicine, CRISPR, skin and connective tissue diseases, 030217 neurology & neurosurgery, 030304 developmental biology, medicine.drug
Abstract

Interferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identified DAXX, a scaffold protein residing in PML nuclear bodies known to limit the replication of DNA viruses and retroviruses, as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells. Basal expression of DAXX was sufficient to limit the replication of SARS-CoV-2, and DAXX over-expression further restricted infection. In contrast with most of its previously described antiviral activities, DAXX-mediated restriction of SARS-CoV-2 was independent of the SUMOylation pathway. SARS-CoV-2 infection triggered the re-localization of DAXX to cytoplasmic sites and promoted its degradation. Mechanistically, this process was mediated by the viral papain-like protease (PLpro) and the proteasome. Together, these results demonstrate that DAXX restricts SARS-CoV-2, which in turn has evolved a mechanism to counteract its action.

Published
2021

12. Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Author

Olivier Schwartz, Cyril Planchais, Aurélie Velay, Françoise Porrot, Thierry Prazuck, Laura Courtellemenont, Matthieu Prot, Julien Le Guen, Maaran Michael Rajah, Julien Puech, Hugo Mouquet, Floriane Gallais, Aymeric Sève, Florence Guivel-Benhassine, Laurent Hocqueloux, Samira Fafi-Kremer, Etienne Simon-Loriere, Dhiaeddine Edriss, Hélène Péré, Artem Baidaliuk, Félix A. Rey, Delphine Planas, David Veyer, Nicolas Robillard, Timothée Bruel, Najibi Kassis-Chikhani, Laurent Bélec, Isabelle Staropoli, and Pierre Gantner

Subjects
Lineage (genetic), Immune system, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine, biology.protein, Biology, Antibody, Monoclonal antibody, Virology, Epitope, Neutralization
Abstract

The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India1–6. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.

Published
2021

13. A novel SARS-CoV-2 related coronavirus in bats from Cambodia

Author

Putita Ou Tey, Philippe Buchy, Jonna A. K. Mazet, Erik A. Karlsson, Vuong Tan Tu, Tracey Goldstein, Veasna Duong, Christine K. Johnson, Philippe Dussart, Vibol Hul, Etienne Simon-Loriere, Déborah Delaune, Alexandre Hassanin, Fabiana Gámbaro, Lucy Keatts, and Artem Baidaliuk

Subjects
Rhinolophus, Coronavirus disease 2019 (COVID-19), biology, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus diseases, biology.organism_classification, medicine.disease_cause, Geographic distribution, Rhinolophus shameli, Evolutionary biology, Metagenomics, Pandemic, medicine, Coronavirus
Abstract

Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010. Metagenomic sequencing identified nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a small region corresponding to the spike N terminal domain. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously understood, and suggests that Southeast Asia represents a key area to consider in the ongoing search for the origins of SARS-CoV-2, and in future surveillance for coronaviruses.

Published
2021

14. Enhanced Zika virus susceptibility of globally invasive Aedes aegypti populations

Author

Rosemary Sang, Martin N. Mayanja, Van-Mai Cao-Lormeau, Julius J. Lutwama, Fabien Aubry, Oumar Faye, Veasna Duong, Louis Lambrechts, Sampson Otoo, Isabelle Dusfour, Elliott F. Miot, Joel Lutomiah, John-Paul Mutebi, Alain Kohl, Caroline Manet, Anna B. Crist, Artem Baidaliuk, Xavier Montagutelli, Alongkot Ponlawat, Sarah H. Merkling, Igor Filipović, Christophe Paupy, Claudia M. E. Romero-Vivas, Jewelna Akorli, Noah H. Rose, Cheikh Tidiane Diagne, Anubis Vega-Rúa, Richard G. Jarman, Laura B. Dickson, Ousmane Faye, Davy Jiolle, Victor O. Anyango, Carolyn S. McBride, Gordana Rašić, Daria Martynow, Stéphanie Dabo, Massamba Sylla, Amadou A. Sall, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique de la souris - Mouse Genetics, Institut Pasteur [Paris], QIMR Berghofer Medical Research Institute, Princeton University, Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Universidad del Norte, Barranquilla, Unité Transmission, Réservoir et Diversité des Pathogènes [Pasteur Guadeloupe, France] (TReD-Path), Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Vectopôle Amazonien Emile Abonnenc [Cayenne, Guyane française], Institut Pasteur de la Guyane, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre International de Recherches Médicales de Franceville (CIRMF), Uganda Virus Research Institute (UVRI), MRC - University of Glasgow Centre for Virus Research, Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Armed Forces Research Institute of Medical Sciences [Bangkok] (AFRIMS), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), University of Ghana, Kenya Medical Research Institute (KEMRI), Centers for Disease Control and Prevention, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD), Walter Reed Army Institute of Research, Arbovirus et Virus de Fièvres Hémorragiques [Dakar, Sénégal], Institut Pasteur de Dakar, This work was primarily funded by the European Union’s Horizon 2020 research and innovation programme under ZikaPLAN grant agreement no. 734584 (to L.L.). This work was also supported by Agence Nationale de la Recherche (grants ANR-16-CE35-0004-01, ANR-17-ERC2-0016-01, and ANR-18-CE35-0003-01 to L.L.), the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to L.L. and X.M.), the Inception program (Investissement d’Avenir grant ANR-16-CONV-0005 to L.L.), the City of Paris Emergence(s) program in Biomedical Research (to L.L.), the QIMR Berghofer Medical Research Institute (Seed Funding Grant to G.R.), the Programme Opérationnel FEDER-Guadeloupe-Conseil Régional 2014-2020 (grant 2015-FED-192 to A.V.-R.), the European Union's Horizon 2020 research and innovation programme under ZIKALLIANCE grant agreement no. 734548 (to A.V.-R.), the U.S. National Institutes of Health (grant NIDCD R00-DC012069 to C.S.M.), a Helen Hay Whitney Postdoctoral Fellowship (to N.H.R.), the UK Medical Research Council (grant MC_UU_12014/8 to A.K.), and the CDC (J.-P.M.). C.S.M. is a New York Stem Cell Foundation—Robertson Investigator., ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), ANR-17-ERC2-0016,GxG,Base génétique de la spécificité génotype-génotype dans l'interaction naturelle entre un virus et son insecte vecteur(2017), ANR-18-CE35-0003,BAKOUMBA,Dissection de la base génétique d'un phénotype naturel de résistance à la dengue chez le moustique Aedes aegypti(2018), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 734584,ZikaPLAN, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Collège Doctoral

Subjects
viruses, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Population, Zoology, Human pathogen, MESH: Zika Virus, Aedes aegypti, MESH: Host Microbial Interactions, Arbovirus, Zika virus, 03 medical and health sciences, 0302 clinical medicine, MESH: Zika Virus Infection, MESH: Mice, Inbred C57BL, Out of africa, parasitic diseases, medicine, MESH: Animals, Zoonotic virus, education, MESH: Mice, 030304 developmental biology, 0303 health sciences, education.field_of_study, Multidisciplinary, MESH: Humans, biology, fungi, virus diseases, MESH: Aedes, biology.organism_classification, medicine.disease, 3. Good health, Vector (epidemiology), MESH: Mosquito Vectors
Abstract

Domesticating Zika virus Why hasn't Zika virus (ZIKV) disease caused as much devastation in Africa, its continent of origin, as it has in the Americas? Outside of Africa, this flavivirus is transmitted by a ubiquitous mosquito subspecies, Aedes aegypti aegypti , which emerged from the African forerunner subspecies A. aegypti formosus and acquired a preference for human blood and a peridomestic lifestyle. Now, this subspecies colonizes many intertropical cities, aided by climate change and human trash. Aubry et al. tested 14 laboratory mosquito colonies for their relative susceptibility to ZIKV. Quantitative trait locus mapping showed differences on chromosome 2 between mosquitoes from Gabon and Guadeloupe. Mouse infection experiments revealed that African mosquitoes transmitted a smaller virus inoculum than the South American insects. Increased susceptibility coupled with the ability of A. aegypti aegypti to breed in any discarded object containing water has amplified the problematic nature of this virus as it has circumnavigated the world. Science , this issue p. 991

Published
2020

15. High transmissibility and fetal pathogenicity of recent Zika virus strains from the African lineage

Author

Maïlis Darmuzey, Natapong Jupatanakul, Ousmane Faye, Suzanne J.F. Kaptein, Leen Delang, Caroline Manet, Maxime Gilsoul, Cheikh Tidiane Diagne, Richard G. Jarman, Stéphanie Dabo, Johan Neyts, Elliott F. Miot, Albin Fontaine, Fabiana Gámbaro, Artem Baidaliuk, Laurent Nguyen, Etienne Simon-Loriere, Sofie Jacobs, Xavier Montagutelli, Louis Lambrechts, Van-Mai Cao-Lormeau, Oumar Faye, Claudia M. E. Romero-Vivas, Sebastian Lequime, Amadou A. Sall, and Fabien Aubry

Subjects
Fetus, Microcephaly, medicine, Outbreak, Fetal loss, Biology, biology.organism_classification, Pathogenicity, medicine.disease, Virology, Virus, Zika virus, Immunocompetent mouse
Abstract

SummaryThe global emergence of Zika virus (ZIKV) in the last decade revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects such as microcephaly. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compared the transmissibility and pathogenicity of seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We found that recent African ZIKV strains largely outperformed their Asian counterparts in mosquito transmission kinetics experiments, which translated into a markedly higher epidemic potential in outbreak computer simulations. In addition, African ZIKV strains were significantly more lethal than Asian ZIKV strains in immunocompromised adult mice. Finally, prenatal infection of immunocompetent mouse embryos with an African ZIKV strain resulted in embryonic death whereas it caused microcephaly with Asian ZIKV strains. Together, our results demonstrate the high epidemic potential and pathogenicity of recent ZIKV strains from Africa. Importantly, they also imply that the African ZIKV lineage could more easily go unnoticed by public health surveillance systems than the Asian ZIKV lineage due to its propensity to cause fetal loss rather than birth defects.

Published
2020

16. Introductions and early spread of SARS-CoV-2 in France, 24 January to 23 March 2020

Author

Mélanie Albert, Fawzi Derrar, Sylvie Behillil, Flora Donati, Sylvie van der Werf, Marion Barbet, Andreea Alexandru, Etienne Simon-Loriere, Fabiana Gámbaro, Angela Brisebarre, Maud Vanpeene, Artem Baidaliuk, Meline Bizard, Vincent Enouf, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), 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), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), National Influenza Center, Viral Respiratory Laboratory [Alger], This study has received funding from Institut Pasteur, CNRS, Université de Paris, Santé publique France, the French Government's Investissement d'Avenir programme, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), France Génomique (ANR-10-INBS-09-09), IBISA, and the RECOVER project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 101003589. ESL acknowledges funding from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
0301 basic medicine, MESH: Coronavirus Infections, Epidemiology, [SDV]Life Sciences [q-bio], phylogeny, Disease Outbreaks, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Coronavirus, outbreak surveillance, MESH: COVID-19, 030212 general & internal medicine, MESH: Disease Outbreaks, MESH: Phylogeny, Clade, virus genomics, Phylogenetic tree, biology, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), 3. Good health, Geography, MESH: RNA, Viral, MESH: Sentinel Surveillance, RNA, Viral, MESH: Betacoronavirus, France, MESH: Genome, Viral, Coronavirus Infections, Sequence Analysis, Rapid Communication, MESH: Pandemics, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Zoology, Genome, Viral, Betacoronavirus, Viral Proteins, MESH: Sequence Analysis, 03 medical and health sciences, Virology, Humans, MESH: SARS-CoV-2, Pandemics, MESH: Humans, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, biology.organism_classification, MESH: Viral Proteins, Coronavirus, MESH: France, 030104 developmental biology, MESH: Pneumonia, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sentinel Surveillance
Abstract

International audience; Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.

Published
2020

17. Enhanced Zika virus susceptibility of globally invasive

Author

Fabien, Aubry, Stéphanie, Dabo, Caroline, Manet, Igor, Filipović, Noah H, Rose, Elliott F, Miot, Daria, Martynow, Artem, Baidaliuk, Sarah H, Merkling, Laura B, Dickson, Anna B, Crist, Victor O, Anyango, Claudia M, Romero-Vivas, Anubis, Vega-Rúa, Isabelle, Dusfour, Davy, Jiolle, Christophe, Paupy, Martin N, Mayanja, Julius J, Lutwama, Alain, Kohl, Veasna, Duong, Alongkot, Ponlawat, Massamba, Sylla, Jewelna, Akorli, Sampson, Otoo, Joel, Lutomiah, Rosemary, Sang, John-Paul, Mutebi, Van-Mai, Cao-Lormeau, Richard G, Jarman, Cheikh T, Diagne, Oumar, Faye, Ousmane, Faye, Amadou A, Sall, Carolyn S, McBride, Xavier, Montagutelli, Gordana, Rašić, and Louis, Lambrechts

Subjects
Mice, Inbred C57BL, Mice, Host Microbial Interactions, Aedes, Zika Virus Infection, Animals, Humans, Mosquito Vectors, Zika Virus
Abstract

The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito

Published
2020

18. Novel genome sequences of cell-fusing agent virus allow comparison of virus phylogeny with the genetic structure of

Author

Artem, Baidaliuk, Sébastian, Lequime, Isabelle, Moltini-Conclois, Stéphanie, Dabo, Laura B, Dickson, Matthieu, Prot, Veasna, Duong, Philippe, Dussart, Sébastien, Boyer, Chenyan, Shi, Jelle, Matthijnssens, Julien, Guglielmini, Andrea, Gloria-Soria, Etienne, Simon-Lorière, and Louis, Lambrechts

Subjects
Aedes aegypti, viruses, insect-specific virus, phylogenetic analysis, fungi, virus diseases, Research Article
Abstract

Flaviviruses encompass not only medically relevant arthropod-borne viruses (arboviruses) but also insect-specific flaviviruses (ISFs) that are presumably maintained primarily through vertical transmission in the insect host. Interestingly, ISFs are commonly found infecting important arbovirus vectors such as the mosquito Aedes aegypti. Cell-fusing agent virus (CFAV) was the first described ISF of mosquitoes more than four decades ago. Despite evidence for widespread CFAV infections in A.aegypti populations and for CFAV potential to interfere with arbovirus transmission, little is known about CFAV evolutionary history. Here, we generated six novel CFAV genome sequences by sequencing three new virus isolates and subjecting three mosquito samples to untargeted viral metagenomics. We used these new genome sequences together with published ones to perform a global phylogenetic analysis of CFAV genetic diversity. Although there was some degree of geographical clustering among CFAV sequences, there were also notable discrepancies between geography and phylogeny. In particular, CFAV sequences from Cambodia and Thailand diverged significantly, despite confirmation that A.aegypti populations from both locations are genetically close. The apparent phylogenetic discrepancy between CFAV and its A.aegypti host in Southeast Asia indicates that other factors than host population structure shape CFAV genetic diversity.

Published
2020

19. Introductions and early spread of SARS-CoV-2 in France

Author

Meline Bizard, Etienne Simon-Loriere, Andreea Alexandru, Sylvie van der Werf, Vincent Enouf, Flora Donati, Marion Barbet, Maud Vanpeene, Artem Baidaliuk, Fabiana Gámbaro, Angela Brisebarre, Fawzi Derrar, Sylvie Behillil, and Mélanie Albert

Subjects
0303 health sciences, Coronavirus disease 2019 (COVID-19), 030306 microbiology, Transmission (medicine), Genomic data, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, Biology, medicine.disease_cause, Virology, Virus, 3. Good health, 03 medical and health sciences, medicine, Clade, 030304 developmental biology, Coronavirus
Abstract

Following the emergence of coronavirus disease (COVID-19) in Wuhan, China in December 2019, specific COVID-19 surveillance was launched in France on January 10, 2020. Two weeks later, the first three imported cases of COVID-19 into Europe were diagnosed in France. We sequenced 97 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from samples collected between January 24 and March 24, 2020 from infected patients in France. Phylogenetic analysis identified several early independent SARS-CoV-2 introductions without local transmission, highlighting the efficacy of the measures taken to prevent virus spread from symptomatic cases. In parallel, our genomic data reveals the later predominant circulation of a major clade in many French regions, and implies local circulation of the virus in undocumented infections prior to the wave of COVID-19 cases. This study emphasizes the importance of continuous and geographically broad genomic sequencing and calls for further efforts with inclusion of asymptomatic infections.

Published
2020

20. Non-retroviral endogenous viral element limits cognate virus replication in Aedes aegypti ovaries

Author

Sebastian Lequime, Maria-Carla Saleh, Albin Fontaine, Louis Lambrechts, Artem Baidaliuk, Ronald P. van Rij, Anna B. Crist, Sarah H. Merkling, Yasutsugu Suzuki, Hervé Blanc, Isabelle Moltini-Conclois, Lionel Frangeul, Pascal Miesen, Virus et Interférence ARN - Viruses and RNA Interference, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Collège Doctoral, Sorbonne Université (SU), Radboud University Medical Center [Nijmegen], Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), R.P.v.R. was supported by the Netherlands Organisation for Scientific Research (VICI grant 016.VICI.170.090). P.M. was supported by a short-term fellowship of the European Molecular Biology Organization (EMBO grant ASTF 449-2016). Work in the laboratory of L.L. was supported by Agence Nationale de la Recherche (grants ANR-16-CE35-0004-01 and ANR-17-ERC2-0016-01) and the City of Paris Emergence(s) program in Biomedical Research. Work in the laboratory of M.-C.S. was supported by the European Research Council (FP7/2013-2019 ERC CoG 615220). L.L. and M.-C.S. were financed by the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID)., We thank Catherine Lallemand for assistance with mosquito rearing and Fabien Aubry for technical aid during review. We are grateful to Catherine Bourgouin and Nicolas Puchot for assistance with the microinjection apparatus and to Anavaj Sakuntabhai for facilitation of the mosquito genome sequencing., ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), ANR-17-ERC2-0016,GxG,Base génétique de la spécificité génotype-génotype dans l'interaction naturelle entre un virus et son insecte vecteur(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 615220,EC:FP7:ERC,ERC-2013-CoG,RNAIMMUNITY(2015), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], and Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, insect-specific flavivirus, animal structures, [SDV]Life Sciences [q-bio], viruses, Genome, Insect, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], mosquito, Aedes aegypti, Biology, Virus Replication, Genome, General Biochemistry, Genetics and Molecular Biology, Virus, 03 medical and health sciences, Viral Proteins, 0302 clinical medicine, RNA interference, Genome editing, Aedes, CRISPR, Animals, RNA, Small Interfering, 030304 developmental biology, insect immunity, 0303 health sciences, siRNA pathway, Cas9, piRNA pathway, Flavivirus, 030302 biochemistry & molecular biology, fungi, cell-fusing agent virus, biology.organism_classification, Virology, 3. Good health, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Viral replication, endogenous viral element, embryonic structures, RNA, Viral, Female, CRISPR-Cas9, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 225985.pdf (Publisher’s version ) (Open Access) Endogenous viral elements (EVEs) are viral sequences integrated in host genomes. A large number of non-retroviral EVEs was recently detected in Aedes mosquito genomes, leading to the hypothesis that mosquito EVEs may control exogenous infections by closely related viruses. Here, we experimentally investigated the role of an EVE naturally found in Aedes aegypti populations and derived from the widespread insect-specific virus, cell-fusing agent virus (CFAV). Using CRISPR-Cas9 genome editing, we created an Ae. aegypti line lacking the CFAV EVE. Absence of the EVE resulted in increased CFAV replication in ovaries, possibly modulating vertical transmission of the virus. Viral replication was controlled by targeting of viral RNA by EVE-derived P-element-induced wimpy testis-interacting RNAs (piRNAs). Our results provide evidence that antiviral piRNAs are produced in the presence of a naturally occurring EVE and its cognate virus, demonstrating a functional link between non-retroviral EVEs and antiviral immunity in a natural insect-virus interaction.

Published
2020
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21. Novel genome sequences of cell-fusing agent virus allow comparison of virus phylogeny with the genetic structure of Aedes aegypti populations

Author

Sebastian Lequime, Laura B. Dickson, Jelle Matthijnssens, Julien Guglielmini, Veasna Duong, Sébastien Boyer, Artem Baidaliuk, Andrea Gloria-Soria, Isabelle Moltini-Conclois, Louis Lambrechts, Matthieu Prot, Stéphanie Dabo, Philippe Dussart, Etienne Simon-Loriere, Chenyan Shi, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris], Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Réseau International des Instituts Pasteur (RIIP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Yale University [New Haven], The Connecticut Agricultural Experiment Station [New Haven] (CAES), This work was supported by Agence Nationale de la Recherche (grant numbers ANR-16-CE35-0004-01 and ANR-17-ERC2-0016-01), the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant number ANR-10-LABX-62-IBEID), the INCEPTION program (Investissements d’Avenir grant number ANR-16-CONV-0005), the City of Paris Emergence(s) program in Biomedical Research, and the European Union Seventh Framework Programme (FP7/2007/2011) under Grant Agreement 282378., We thank Catherine Lallemand for assistance with mosquito rearing, and Jeff Powell, Carla Saleh, and Marie Flamand for their insights. We are grateful to Martin Mayanja and Julius Lutwama for providing the original mosquito colony from Uganda. We thank Gordana Rašić, Lícia Natal Fernandes, Bronwyn MacInnis, and Hayden Metsky for providing CFAV sequences. We thank Oliver Pybus, Peter Simmonds, Xavier de Lamballerie, and one anonymous reviewer for their insights and constructive suggestions on earlier versions of the manuscript, ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-ERC2-0016,GxG,Base génétique de la spécificité génotype-génotype dans l'interaction naturelle entre un virus et son insecte vecteur(2017), European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, and Institut Pasteur [Paris] (IP)

Subjects
Viral metagenomics, viruses, insect-specific virus, 030231 tropical medicine, Aedes aegypti, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Microbiology, Arbovirus, Genome, 03 medical and health sciences, 0302 clinical medicine, Phylogenetics, Virology, medicine, 030304 developmental biology, 0303 health sciences, Genetic diversity, biology, Phylogenetic tree, phylogenetic analysis, fungi, virus diseases, biology.organism_classification, medicine.disease, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Evolutionary biology, Genetic structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract

Flaviviruses encompass not only medically relevant arthropod-borne viruses (arboviruses) but also insect-specific flaviviruses (ISFs) that are presumably maintained primarily through vertical transmission in the insect host. Interestingly, ISFs are commonly found infecting important arbovirus vectors such as the mosquito Aedes aegypti. Cell-fusing agent virus (CFAV) was the first described ISF of mosquitoes more than four decades ago. Despite evidence for widespread CFAV infections in A.aegypti populations and for CFAV potential to interfere with arbovirus transmission, little is known about CFAV evolutionary history. Here, we generated six novel CFAV genome sequences by sequencing three new virus isolates and subjecting three mosquito samples to untargeted viral metagenomics. We used these new genome sequences together with published ones to perform a global phylogenetic analysis of CFAV genetic diversity. Although there was some degree of geographical clustering among CFAV sequences, there were also notable discrepancies between geography and phylogeny. In particular, CFAV sequences from Cambodia and Thailand diverged significantly, despite confirmation that A.aegypti populations from both locations are genetically close. The apparent phylogenetic discrepancy between CFAV and its A.aegypti host in Southeast Asia indicates that other factors than host population structure shape CFAV genetic diversity. ispartof: VIRUS EVOLUTION vol:6 issue:1 ispartof: location:England status: published

Published
2020

22. A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

Author

Sylvie van der Werf, Anna Zhukova, Etienne Simon-Loriere, Elena Guillotel, Pierre Fillâtre, Alice Gabellec, Artem Baidaliuk, François-Xavier Lescure, Rodolphe Buzelé, Dominique Costagliola, Bertrand Gagnière, Vincent Enouf, Vincent Thibault, Pascale Reusse, Véronique Merour, Marion Valence, Sylvie Behillil, Catherine Montagne, Marie-José Dufour, Claire Grolhier, Charlotte Pronier, Pierre Tattevin, Mathieu Tourdjman, Rémi Vatan, Nicolas Velmans, Edith Droumaguet, Sophie Geffroy Du Coudret, and Nicolas Massart

Subjects
Microbiology (medical), 0303 health sciences, medicine.medical_specialty, business.industry, Outbreak, General Medicine, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Real-time polymerase chain reaction, medicine.anatomical_structure, Interquartile range, Internal medicine, Severity of illness, medicine, Observational study, 030212 general & internal medicine, Seroconversion, Respiratory system, 10. No inequality, business, 030304 developmental biology, Respiratory tract
Abstract

Objectives In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a ‘variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. Methods Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. Results From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73–88 versus 73 years, IQR 67–82, p Conclusion We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

Published
2022

23. Cell-Fusing Agent Virus Reduces Arbovirus Dissemination in Aedes aegypti Mosquitoes In Vivo

Author

Louis Lambrechts, Van-Mai Cao-Lormeau, Sarah H. Merkling, Isabelle Moltini-Conclois, Fanny Delaigue, Elliott F. Miot, Fabien Aubry, Artem Baidaliuk, Laura B. Dickson, Stéphanie Dabo, Sebastian Lequime, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD), This work was supported by the Agence Nationale de la Recherche (grants ANR-16-CE35-0004-01 and ANR-17-ERC2-0016-01), the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID), the European Union’s Horizon 2020 research and innovation program under ZikaPLAN grant agreement no. 734584, and the City of Paris Emergence(s) Program in Biomedical Research., We thank Catherine Lallemand for assistance with mosquito rearing. We are grateful to Carla Saleh, Marie Flamand, Yasutsugu Suzuki, Laura Levi, Clément Dubois, and two anonymous reviewers for their insights. We thank Thanyalak Fansiri and Alongkot Ponlawat for the initial field sampling of mosquitoes in Thailand. We are grateful to the blood donor volunteers for participation in this study and the ICAReB staff for its support., ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), ANR-17-ERC2-0016,GxG,Base génétique de la spécificité génotype-génotype dans l'interaction naturelle entre un virus et son insecte vecteur(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 734584,ZikaPLAN, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège Doctoral

Subjects
viruses, insect-specific virus, viral interference, Dengue virus, Virus Replication, medicine.disease_cause, Dengue fever, Zika virus, Dengue, Aedes aegypti, Aedes, Spotlight, Viral Interference, Phylogeny, 0303 health sciences, biology, Zika Virus Infection, virus diseases, 3. Good health, Flavivirus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immunology, Insect Viruses, Mosquito Vectors, Microbiology, Arbovirus, Virus, Cell Line, superinfection, 03 medical and health sciences, Virology, medicine, Animals, Humans, 030304 developmental biology, 030306 microbiology, fungi, Zika Virus, Dengue Virus, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, coinfection, arbovirus, Genetic Diversity and Evolution, Insect Science, Arboviruses
Abstract

The mosquito Aedes aegypti carries several arthropod-borne viruses (arboviruses) that are pathogenic to humans, including dengue and Zika viruses. Interestingly, A. aegypti is also naturally infected with insect-only viruses, such as cell-fusing agent virus. Although interactions between cell-fusing agent virus and dengue virus have been documented in mosquito cells in culture, whether wild strains of cell-fusing agent virus interfere with arbovirus transmission by live mosquitoes was unknown. We used an experimental approach to demonstrate that cell-fusing agent virus infection reduces the propagation of dengue and Zika viruses in A. aegypti mosquitoes. These results support the idea that insect-only viruses in nature can modulate the ability of mosquitoes to carry arboviruses of medical significance and that they could possibly be manipulated to reduce arbovirus transmission., Aedes aegypti mosquitoes are the main vectors of arthropod-borne viruses (arboviruses) of public health significance, such as the flaviviruses dengue virus (DENV) and Zika virus (ZIKV). Mosquitoes are also the natural hosts of a wide range of viruses that are insect specific, raising the question of their influence on arbovirus transmission in nature. Cell-fusing agent virus (CFAV) was the first described insect-specific flavivirus, initially discovered in an A. aegypti cell line and subsequently detected in natural A. aegypti populations. It was recently shown that DENV and the CFAV strain isolated from the A. aegypti cell line have mutually beneficial interactions in mosquito cells in culture. However, whether natural strains of CFAV and DENV interact in live mosquitoes is unknown. Using a wild-type CFAV isolate recently derived from Thai A. aegypti mosquitoes, we found that CFAV negatively interferes with both DENV type 1 and ZIKV in vitro and in vivo. For both arboviruses, prior infection by CFAV reduced the dissemination titer in mosquito head tissues. Our results indicate that the interactions observed between arboviruses and the CFAV strain derived from the cell line might not be a relevant model of the viral interference that we observed in vivo. Overall, our study supports the hypothesis that insect-specific flaviviruses may contribute to reduce the transmission of human-pathogenic flaviviruses. IMPORTANCE The mosquito Aedes aegypti carries several arthropod-borne viruses (arboviruses) that are pathogenic to humans, including dengue and Zika viruses. Interestingly, A. aegypti is also naturally infected with insect-only viruses, such as cell-fusing agent virus. Although interactions between cell-fusing agent virus and dengue virus have been documented in mosquito cells in culture, whether wild strains of cell-fusing agent virus interfere with arbovirus transmission by live mosquitoes was unknown. We used an experimental approach to demonstrate that cell-fusing agent virus infection reduces the propagation of dengue and Zika viruses in A. aegypti mosquitoes. These results support the idea that insect-only viruses in nature can modulate the ability of mosquitoes to carry arboviruses of medical significance and that they could possibly be manipulated to reduce arbovirus transmission.

Published
2019

24. Worldwide survey reveals lower susceptibility of African Aedes aegypti mosquitoes to diverse strains of Zika virus

Author

Fabien Aubry, Daria Martynow, Artem Baidaliuk, Sarah H. Merkling, Laura B. Dickson, Claudia M. Romero-Vivas, Anubis Vega-Rúa, Isabelle Dusfour, Davy Jiolle, Christophe Paupy, Martin N. Mayanja, Julius J. Lutwama, Alain Kohl, Veasna Duong, Alongkot Ponlawat, Van-Mai Cao-Lormeau, Richard G. Jarman, Cheikh T. Diagne, Oumar Faye, Ousmane Faye, Amadou A. Sall, and Louis Lambrechts

Subjects
0303 health sciences, Range (biology), Transmission (medicine), 030231 tropical medicine, Outbreak, Zoology, Aedes aegypti, Biology, 16. Peace & justice, biology.organism_classification, 3. Good health, Zika virus, 03 medical and health sciences, Flavivirus, 0302 clinical medicine, Vector (epidemiology), Enzootic, 030304 developmental biology
Abstract

Zika virus (ZIKV) is a flavivirus mainly transmitted to humans through the bite of infected Aedes aegypti mosquitoes. First isolated in Uganda in 1947, ZIKV was shown to circulate in enzootic sylvatic cycles in Africa and Asia for at least half a century before the first reported human epidemic occurred in 2007 on the Pacific island of Yap, Micronesia. Subsequently, larger ZIKV outbreaks were recorded in French Polynesia and other South Pacific islands during 2013-2014. In 2015, ZIKV reached Brazil from where it rapidly spread across the Americas and the Caribbean, causing hundreds of thousands of human cases. The factors that have fueled the explosiveness and magnitude of ZIKV emergence in the Pacific and the Americas are poorly understood. Reciprocally, the lack of major human epidemics of ZIKV in regions with seemingly favorable conditions, such as Africa or Asia, remains largely unexplained. To evaluate the potential contribution of vector population diversity to ZIKV epidemiological patterns, we established dose-response curves for eight field-derived Ae. aegypti populations representing the global range of the species, following experimental exposure to six low-passage ZIKV strains spanning the current viral genetic diversity. Our results reveal that African Ae. aegypti are significantly less susceptible than non-African Ae. aegypti across all ZIKV strains tested. We suggest that low susceptibility of vector populations may have contributed to prevent large-scale human transmission of ZIKV in Africa.

Published
2018

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