Restriction of Retroviruses by TRIM5α

Despite multiple transfers of primate lentiviruses to humans, the current AIDS pandemic has resulted from a single zoonosis of simian immunodeficiency virus from chimpanzees. The rarity of successful zoonosis is due to effective species barriers that are mediated partly by dominant antiviral factors, termed restriction factors. The tripartite motif protein TRIM5α has emerged as an important restriction factor controlling species-specific retroviral replication. TRIM5α was identified as an antiviral factor, active against HIV-1, in rhesus macaques. Subsequently, it was shown to encode previously described antiviral factors in humans (Ref1) and monkeys (Lv1). TRIM5α causes a block to sensitive retroviral infection after viral entry into the target cell and usually before viral DNA synthesis. This review considers the role of TRIM5α as an antiviral protein in mammals. Recent results from mutational analysis of TRIM5α and their contribution to a mechanistic model for TRIM5α antiviral activity are discussed, as is the future for postentry restriction factors.