1. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5[alpha] restriction factor
- Author
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Stremlau, Matthew, Perron, Michel, Lee, Mark, Li, Yuan, Song, Byeongwoon, Javanbakht, Hassan, Diaz-Griffero, Felipe, Anderson, Donovan J., Sundquist, Wesley I., and Sodroski, Joseph
- Subjects
HIV (Viruses) -- Structure ,HIV (Viruses) -- Analysis ,Natural immunity -- Research ,Science and technology - Abstract
The host restriction factor TRIM5[alpha] mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5[alpha] variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5[alpha] B30.2 domain. Human and New World monkey TRIM5[alpha] proteins associated less efficiently with the HIV-1 capsid, accounting for the lack of restriction in cells of these species. After infection, the expression of a restricting TRIM5[alpha] in the target cells correlated with a decrease in the amount of particulate capsid in the cytosol. In some cases, this loss of particulate capsid was accompanied by a detectable increase in soluble capsid protein. Inhibiting the proteasome did not abrogate restriction. Thus, TRIM5[alpha] restricts retroviral infection by specifically recognizing the capsid and promoting its rapid, premature disassembly. B30.2(SPRY) domain | tripartite motif | HIV-1 | RING, B-box, and coiled-coil protein | innate immunity
- Published
- 2006