Abstract
It is of great interest to understand the molecular details of the pathways that constitute species barriers to viral infection. The tripartite motif protein TRIM5alpha has emerged as an important mediator of species-specific retroviral replication and innate immunity. This review considers the role of TRIM5alpha as an antiviral protein in mammals. The methods used to identify species-specific restriction to retroviral infection, and the identification of TRIM5alpha itself, are outlined. TRIM5alpha mediates an early postentry block to sensitive retroviral infection, usually before viral DNA synthesis. Results from mutational analysis of TRIM5alpha and their contribution to a mechanistic model for TRIM5alpha antiviral activity are discussed. The antiviral role of other TRIM proteins is considered, as is the role of TRIM5alpha cytoplasmic bodies.