Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells
Sophie‐Marie Aicher, Félix Streicher, Maxime Chazal, Delphine Planas, Dongsheng Luo, Julian Buchrieser, Monika Němcová, Veronika Seidlova, Jan Zukal, Jordi Serra‐Cobo, Dominique Pontier, Bertrand Pain, Gert Zimmer, Olivier Schwartz, Philippe Roingeard, Jiří Pikula, Laurent Dacheux, Nolwenn Jouvenet
Abstract
Bats are host ancestors of several viruses that cause serious disease in humans, as illustrated by the ongoing SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions has been hampered by a limited number of available bat cellular models. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The various permissivities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by overexpression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bat cells and viruses.