TRIM5α restricts poxviruses and is antagonized by CypA and the viral protein C6.

ABSTRACT: Human tripartite motif protein 5α (TRIM5α) is a well-characterized restriction factor for some RNA viruses, including HIV^1-5; however, reports are limited for DNA viruses^6,7. Here we demonstrate that TRIM5α also restricts orthopoxviruses and, via its SPRY domain, binds to the orthopoxvirus capsid protein L3 to diminish virus replication and activate innate immunity. In response, several orthopoxviruses, including vaccinia, rabbitpox, cowpox, monkeypox, camelpox and variola viruses, deploy countermeasures. First, the protein C6 binds to TRIM5 via the RING domain to induce its proteasome-dependent degradation. Second, cyclophilin A (CypA) is recruited via interaction with the capsid protein L3 to virus factories and virions to antagonize TRIM5α; this interaction is prev

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC10447239 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature