Enterovirus 3C Protease Cleaves TRIM7 To Dampen Its Antiviral Activity

Wenchun Fan, Matthew B. McDougal, John W. Schoggins

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mammalian TRIM7 is an antiviral protein that inhibits multiple human enteroviruses by degrading the viral 2BC protein. Whether TRIM7 is reciprocally targeted by enteroviruses is not known. Here, we report that the 3C protease (3Cpro) from two enteroviruses, coxsackievirus B3 (CVB3) and poliovirus, targets TRIM7 for cleavage. CVB3 3Cpro cleaves TRIM7 at glutamine 24 (Q24), resulting in a truncated TRIM7 that fails to inhibit CVB3 due to dampened E3 ubiquitin ligase activity. TRIM7 Q24 is highly conserved across mammals, except in marsupials, which instead have a naturally occurring histidine (H24) that is not subject to 3Cpro cleavage. Marsupials also express two isoforms of TRIM7, and the two proteins from koalas have distinct antiviral activities. The longer isoform contains an additional exon due to alternate splice site usage. This additional exon contains a unique 3Cpro cleavage site, suggesting that certain enteroviruses may have evolved to target marsupial TRIM7 even if the canonical Q24 is missing. Combined with computational analyses indicating that TRIM7 is rapidly evolving, our data raise the possibility that TRIM7 may be targeted by enterovirus evasion strategies and that evolution of TRIM7 across mammals may have conferred unique antiviral properties.

Original languageEnglish (US)
JournalJournal of virology
Volume96
Issue number19
DOIs
StatePublished - Oct 2022
Externally publishedYes

Keywords

  • 3C protease
  • TRIM7
  • coxsackievirus B3
  • mammals
  • marsupials
  • virus-host interaction
  • virus-host interactions

ASJC Scopus subject areas

  • Insect Science
  • Virology
  • Microbiology
  • Immunology

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