Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling.

ABSTRACT: RHIM is a protein motif facilitating the assembly of large signaling complexes triggering regulated cell death. A few DNA viruses employ viral RHIMs mimicking host RHIMs and counteract cell death by interacting with host RHIM-proteins to alleviate antiviral defenses. Whether RNA viruses operate such viral RHIMs remains unknown. Here, we identified viral RHIMs in Nsp13 of SARS-CoV-2 and other bat RNA viruses, providing the basis for bats as the hosts for their evolution. Nsp13 promoted viral RHIM and RNA-binding channel-dependent cell death. However, Nsp13 viral RHIM is more critical for human cell death than in bat-derived Tb1 Lu cells, suggesting species-specific regulation. Nsp13 showed RHIM-dependent interactions with ZBP1 and RIPK3, forming large complexes and promoting ZBP1-RIPK3 sign

SUBMITTER: Mishra S 

PROVIDER: S-EPMC11652944 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature