Antiretroviral potential of human tripartite motif-5 and related proteins

Abstract

TRIM5α is a potent inhibitor of infection by diverse retroviruses and is encoded by one of a large family of TRIM genes. We found that several TRIM motifs among a panel of selected human TRIM proteins (TRIM1, 5, 6, 18, 19, 21 22, 34) could inhibit infection when artificially targeted to an incoming HIV-1 capsid. Conversely, when ectopically expressed as authentic full-length proteins, most lacked activity against a panel of retroviruses. The exceptions were TRIM1, TRIM5 and TRIM34 proteins. Weak but specific inhibition of HIV-2/SIV MAC and EIAV by TRIM34 was noted, and human TRIM5α modestly, but specifically, inhibited an HIV-1 strain carrying a mutation in the cyclophilin binding loop (G89V). Restriction activity observed in ectopic expression assays was sometimes not detectable in corresponding RNAi-based knockdown experiments. However, endogenous owl monkey TRIMCyp potently inhibited an SIV AGM strain. Overall, sporadic examples of intrinsic antiretroviral activity exist in this panel of TRIM proteins.