Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells

• Published in: Journal of Virology
• Main Authors: Aicher, Sophie-Marie, Streicher, Felix, Chazal, Maxime, Planas, Delphine, Luo, Dongsheng, Buchrieser, Julian, Nemcova, Monika, Seidlova, Veronika, Zukal, Jan, Serra-Cobo, Jordi, Pontier, Dominique, Pain, Bertrand, Zimmer, Gert, Schwartz, Olivier, Roingeard, Philippe, Pikula, Jiri, Dacheux, Laurent, Jouvenet, Nolwenn
• Other Authors: Signalisation antivirale - Virus sensing and signaling, 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), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur Paris (IP)-Université Paris Cité (UPCité), University of Veterinary and Pharmaceutical Sciences Brno (VFU), Universitat de Barcelona (UB), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universität Bern / University of Bern (UNIBE), Institute of Virology and Immunology Mittelhäusern (IVI), Morphogénèse et antigénicité du VIH, des Virus des Hépatites et Emergents (MAVIVHe), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was funded by the CNRS (N.J. and O.S.), Institut Pasteur (N.J., L.D., and O.S.), the "Urgence COVID-19" fundraising campaign of Institut Pasteur (N.J., L.D., and O.S.), the University of Veterinary Sciences Brno (FVHE/Pikula/ITA2021) (J.P.), the FINOVI Fondation (AO13) and Covid IDEX Universite Lyon 1 (B.P.), LabEx Ecofect (ANR-11-LABX-0048) (Do.P.), Labex IBEID (ANR-10-LABX-62-IBEID) (O.S.), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 (O.S.), and IDISCOVR (O.S.). S.-M.A. and De.P. are supported by the Pasteur-Paris University International Ph.D. Program and the Vaccine Research Institute (ANR-10-LABX-77), respectively. D.L. was funded by the Chinese Scholarship Council and Institut Pasteur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2022
• Subjects: SARS-CoV-2; bat cells; coronavirus; innate immunity; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; Nyctalus noctula
• Online Access: https://hal.inrae.fr/hal-03746441; https://hal.inrae.fr/hal-03746441v2/document; https://hal.inrae.fr/hal-03746441v2/file/2021.05.31.446374.full.pdf; https://doi.org/10.1128/jvi.00608-22

International audience Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that the restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or the absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication, which correlated with a potent interferon response. Our data highlight the existence of species-specific and cell-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses.