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

Abstract

Mammalian cells have developed diverse strategies to restrict retroviral infection1,2,3,4,5. Retroviruses have therefore evolved to counteract such restriction factors, in order to colonize their hosts4,6. 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 disassembly7,8. 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 restriction8,9,10,11. As TRIM5αrh targets incoming mature HIV-1 capsid, but not precursor Gag12, 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.

Cite this article

Sakuma, R., Noser, J., Ohmine, S. et al. Rhesus monkey TRIM5α restricts HIV-1 production through rapid degradation of viral Gag polyproteins. Nat Med 13, 631–635 (2007). https://doi.org/10.1038/nm1562

View full text

>> Full Text:   Rhesus monkey TRIM5α restricts HIV-1 production through rapid degradation of viral Gag polyproteins