Rhesus monkey TRIM5α restricts HIV-1 production through rapid degradation of viral Gag polyproteins

Ryuta Sakuma, Josh A. Noser, Seiga Ohmine, Yasuhiro Ikeda

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Mammalian cells have developed diverse strategies to restrict retroviral infection. Retroviruses have therefore evolved to counteract such restriction factors, in order to colonize their hosts. Tripartite motif-containing 5 isoform-α (TRIM5α) protein from rhesus monkey (TRIM5αrh) restricts human immunodeficiency virus type 1 (HIV-1) infection at a postentry, preintegration stage in the viral life cycle, by recognizing the incoming capsid and promoting its premature disassembly. TRIM5α comprises an RBCC (RING, B-box 2 and coiled-coil motifs) domain and a B30.2(SPRY) domain. Sequences in the B30.2(SPRY) domain dictate the potency and specificity of the restriction. As TRIM5αrh targets incoming mature HIV-1 capsid, but not precursor Gag, it was assumed that TRIM5αrh did not affect HIV-1 production. Here we provide evidence that TRIM5αrh, but not its human ortholog (TRIM5αhu), blocks HIV-1 production through rapid degradation of HIV-1 Gag polyproteins. The specificity for this restriction is determined by sequences in the RBCC domain. Our observations suggest that TRIM5αrh interacts with HIV-1 Gag during or before Gag assembly through a mechanism distinct from the well-characterized postentry restriction. This finding demonstrates a cellular factor blocking HIV-1 production by actively degrading a viral protein. Further understanding of this previously unknown restriction mechanism may reveal new targets for future anti-HIV-1 therapy.

Original languageEnglish (US)
Pages (from-to)631-635
Number of pages5
JournalNature Medicine
Volume13
Issue number5
DOIs
StatePublished - May 1 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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