Species-specific molecular barriers to SARS-CoV-2 replication in bat cells

• 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, schwartz, olivier, Pikula, Jiri, Dacheux, Laurent, Jouvenet, Nolwenn
• Other Authors: Centre National de la Recherche Scientifique (CNRS)
• Format: Report
• Language: English
• Published: HAL CCSD 2021
• Subjects: [SDV]Life Sciences [q-bio]; Nyctalus noctula
• Online Access: https://hal.archives-ouvertes.fr/hal-03448419; https://doi.org/10.1101/2021.05.31.446374

Abstract 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 susceptibility of primary cells from Rhinolophus ferrumequinum and Myotis species, as well as of established and novel cell lines from Myotis myotis , Eptesicus serotinus , Tadarida brasiliensis and Nyctalus noctula , to SARS-CoV-2 infection. None of these cells were sensitive 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 restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or 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. This ability to control viral replication correlated with a potent interferon response. Our data highlight the existence of species-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. Author summary Bats host ancestors of several viruses that cause serious disease in humans, as illustrated by the on-going SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions have been hampered by a limited number of bat cell lines. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The varying susceptibilities 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. ...