Study Probes Bats’ Resistance to Coronavirus Replication

A research collaboration among several European institutions has uncovered the secret to bats’ protection from SARS-CoV-2 replication. Given the concentration of zoonotic viruses that circulate in chiropter populations, the findings have implications for viral research and medical applications.

For years, scientific literature has observed the resistance of some chiropteran species to coronavirus infections. In bats, the immune system is on a pre-alert stage, a condition that allows a faster response to viral infections. For most mammals, having an immune system on a constant pre-alert state would involve inflammation problems but this is not the case for bats, which is why they are the focus of many international epidemiological and immunological studies.

Progress in investigating bat-virus interactions, however, has been hampered by a limited number of available bat cellular models. The current study generated primary cells and cell lines of Rhinolopuhs ferrumequinum, Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis and Nyctalus noctule—species that have been little studied but are found in Europe and Asia. The team analyzed the ability of primary cells from these species to support SARS-CoV-2 replication.

“The results reveal that none of these cells was permissive to the infection, not even those expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), a metallopeptidase that serves as a viral receptor in many mammal species,” says Jordi Serra-Cobo, member of the Department of Evolutionary Biology, Ecology and Environmental Sciences of the University of Barcelona. 

The cells did not allow the infection in the species Rhinolophus ferrumequinum, a chiropteran from the same genus as the Asian bat in which the BANAL-52 virus, a potential ancestor of SARS-CoV-2, was found. The genetic sequences of the BANAL-52 virus is 96.8% similar to that of SARS-CoV-2.

The study contributes to a better understanding of the fighting mechanisms against viral infections. In humans, it is known that the SARS-CoV-2 spike protein binds to the cell membrane receptor ACE2 and then the virus infects the cell. “In the case of the chiropteran cells, either the amount of ACE2 enzyme is small and it no longer enters the cell or, if the virus binds to ACE2, it cannot infect the cell,” says Serra-Cobo.

An important number of zoonotic viruses circulate in chiropter populations without causing symptoms of the disease in the carriers, says Serra-Cobo. “Over the course of the evolutionary history of chiropterans—about 64 million years—there have been processes of coevolution between bats and viruses,” he says.  “One example of these processes is in the adaptation to coronaviruses. The study of the evolutionary adaptations of living beings to deal with viral infections is of great interest, since they provide information that can have medical applications.”

The study was led by experts Nolwenn Jouvenet and Laurent Dacheux, from the Institute Pasteur in Paris and also includes the collaboration of experts from research institutions in France, the Czech Republic and Switzerland. The findings were published recently in Journal of Virology.