Determinants for the rhesus monkey TRIM5α-mediated block of the late phase of HIV-1 replication

Ryuta Sakuma, Seiga Ohmine, Yasuhiro Ikeda

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Rhesus monkey TRIM5α(TRIM5αrh) includes RING, B-box, coiled-coil, and B30.2(PRYSPRY) domains and blocks HIV-1 infection by targeting HIV-1 core through a B30.2(PRYSPRY) domain. Previously, we reported that TRIM5αrh also blocks HIV-1 production in a B30.2(PRYSPRY)-independent manner. Efficient encapsidation of TRIM5αrh, but not human TRIM5α (TRIM5αhu), in HIV-1 virus-like particles suggests the interaction between Gag and TRIM5αrh during viral assembly. Here, we determined responsible regions for late restriction activity of TRIM5αrh. The RING disruption, but not the replacement with human TRIM21 RING, ablated the efficient encapsidation and the late restriction, suggesting that a RING structure was essential for the late restriction and efficient interaction with HIV-1 Gag. The prominent cytoplasmic body formation of TRIM5αrh, which depended on the coiled-coil domain and the ensuing linker 2 region, was not required for the encapsidation. Intriguingly, TRIM5αrh coiled-coil domain mutants (M133T and/or T146A) showed impaired late restriction activity, despite the efficient encapsidation and cytoplasmic body formation. Our results suggest that the TRIM5αrh-mediated late restriction involves at least two distinct activities as follows: (i) interaction with HIV-1 Gag polyprotein through the N-terminal, RING, and B-box 2 regions of a TRIM5αrh monomer, and (ii) an effector function(s) that depends upon the coiled-coil and linker 2 domains of TRIM5αrh. We speculate that the TRIM5αrh coiled-coil region recruits additional factor(s), such as other TRIM family proteins or a cellular protease, during the late restriction. RBCC domains of TRIM family proteins may play a role in sensing newly synthesized viral proteins as a part of innate immunity against viral infection.

Original languageEnglish (US)
Pages (from-to)3784-3793
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number6
DOIs
StatePublished - Feb 5 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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