Recent insights into the mechanism and consequences of TRIM5α retroviral restriction.
The cellular factor TRIM5α inhibits infection by numerous retroviruses in a species-specific manner. The TRIM5α protein from rhesus macaques (rhTRIM5α) restricts infection by HIV-1 while human TRIM5α (huTRIM5α) 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 (TRIM5α 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.
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Jaya
J
Sastri
Edward M
EM
Campbell
D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D009052:Leukemia Virus, Murine / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D012190:Retroviridae / Q000254:growth & development*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases
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