Abstract
The past ten years have seen an explosion of information concerning host restriction factors that inhibit the replication of HIV-1 and other retroviruses. Among these factors is TRIM5, an innate immune signaling molecule that recognizes the capsid lattice as soon as the retrovirion core is released into the cytoplasm of otherwise susceptible target cells. Recognition of the capsid lattice has several consequences that include multimerization of TRIM5 into a complementary lattice, premature uncoating of the virion core, and activation of TRIM5 E3 ubiquitin ligase activity. Unattached, K63-linked ubiquitin chains are generated that activate the TAK1 kinase complex and downstream inflammatory mediators. Polymorphisms in the capsid recognition domain of TRIM5 explain the observed species-specific differences among orthologues and the relatively weak anti-HIV-1 activity of human TRIM5. Better understanding of the complex interaction between TRIM5 and the retrovirus capsid lattice may someday lead to exploitation of this interaction for the development of potent HIV-1 inhibitors.
Highlights
HIV-1 was identified only two years after the first report of AIDS in 1981 [1]
Thanks to these anti-HIV-1 drugs, the number of AIDS cases plummeted in countries like the United States
When HIV-1 and other retroviruses undergo membrane fusion with susceptible target cells, the virion core is released into the target cell cytoplasm
Summary
HIV-1 was identified only two years after the first report of AIDS in 1981 [1]. The first anti-HIV-1 drug, AZT, was approved for patients in 1987, and effective combinations of anti-HIV-1 drugs were in the clinic by the mid-1990s Thanks to these anti-HIV-1 drugs, the number of AIDS cases plummeted in countries like the United States. Despite the impact of basic science on disease in individuals with HIV1 infection, the AIDS pandemic has not gone away. Aside from a small effect in one vaccination trial [7], there is no evidence for prevention of HIV-1 infection in people by a vaccine. According to the UNAIDS report concluding in 2010 (http://www.unaids.org/en/), 34 million people were living with HIV infection, and in that year alone there were 2.7 million new infections
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