Study of retroviral restrictions in a Tadarida bat cell line enlightens specific early blocks and TRIM5 locus multiplication

Bats host many RNA viruses that can potentially cause spillover to humans; however, they rarely develop severe symptoms after infection, suggesting the presence of bat-specific antiviral mechanisms. Although no infectious retroviruses have been isolated from bats, we and other groups have proposed the presence of unknown retrovirus-inhibiting mechanisms in bat cells. In this study, we focused on a particular host factor (TRIM5α) in a specific Yangochiropteran bat cell line that showed resistance to gammaretroviruses; however, its TRIM5α homolog lost its antiretroviral activity, with its ligand-interacting domain retaining the ability to recognize the retrovirus capsid. We identified specific gain-of-function mutations in Yangochiropteran TRIM5α that endow the protein with gammaretrovirus-restricting activity. This finding suggests that during Yangochiropteran evolution, these mutations may have prevented Yangochiropteran TRIM5α from inhibiting gammaretroviruses. Further understanding of retrovirus-inhibiting mechanisms in bat cells would help develop new therapeutic strategies to combat retrovirus-related diseases, such as acquired immunodeficiency syndrome.