Antiretroviral potential of human tripartite motif-5 and related proteins

TRIM5 alpha 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, 2122, 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/SIVMAc and EIAV by TRIM34 was noted, and human TRIM5 a modestly, but specifically, inhibited an HIV-I 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 SIVAGM strain. Overall, sporadic examples of intrinsic antiretroviral activity exist in this panel of TRIM proteins. (c) 2006 Elsevier Inc. All rights reserved.