Anti‐retroviral activity of TRIM5α

Abstract

AbstractHuman immunodeficiency virus type 1 (HIV‐1) shows a very narrow host range limited to humans and chimpanzees. Experimentally, HIV‐1 does not infect Old World monkeys, such as rhesus (Rh) and cynomolgus (CM) monkeys, and fails to replicate in activated CD4 positive T lymphocytes obtained from these monkeys. In contrast, simian immunodeficiency virus isolated from a macaque monkey (SIVmac) can replicate well in both Rh and CM. In 2004, tripartite motif 5α (TRIM5α) was identified as a host factor which plays an important role in the restricted host range of HIV‐1. Rh and CM TRIM5α restrict HIV‐1 infection but not SIVmac, while in comparison, anti‐viral activity of human TRIM5α against those viruses is very weak. TRIM5α consists of the RING, B‐box 2, coiled‐coil and SPRY (B30.2) domains. The RING domain is frequently found in E3 ubiquitin ligase and TRIM5α is degraded via the ubiquitin‐proteasome pathway during HIV‐1 restriction. TRIM5α recognises the multimerised capsid (viral core) of an incoming virus by its α‐isoform specific SPRY domain and is believed to be involved in innate immunity to control retroviral infection. Differences in amino acid sequences in the SPRY domain of TRIM5α of different monkey species were found to affect species‐specific restriction of retrovirus infection, while differences in amino acid sequences in the viral capsid protein determine viral sensitivity to restriction. Accurate structural analysis of the binding surface between the viral capsid protein and TRIM5α SPRY is thus required for the development of new antiretroviral drugs that enhance anti‐HIV‐1 activity of human TRIM5α. Copyright © 2009 John Wiley & Sons, Ltd.