Recent Insights into the Mechanism and Consequences of TRIM5α Retroviral Restriction

The cellular factor TRIM5 alpha inhibits infection by numerous retroviruses in a species-specific manner. The TRIM5 alpha protein from rhesus macaques (rhTRIM5 alpha) restricts infection by HIV-1 while human TRIM5 alpha (huTRIM5 alpha) restricts infection by murine leukemia virus (MLV). In owl monkeys a related protein TRIM-Cyp restricts HIV-1 infection. Several models have been proposed for retroviral restriction by TRIM5 proteins (TRIM5 alpha and TRIM-Cyp). These models collectively suggest that TRIM5 proteins mediate restriction by directly binding to specific determinants in the viral capsid. Through their ability to self-associate TRIM5 proteins compartmentalize the viral capsid core and mediate its abortive disassembly via a poorly understood mechanism that is sensitive to proteasome inhibitors. In this review, we discuss TRIM5-mediated restriction in detail. We also discuss how polymorphisms within human and rhesus macaque populations have been demonstrated to affect disease progression of immunodeficiency viruses in these species.