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Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5514-9. Epub 2006 Mar 15.

Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor.

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  • 1Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School Division of AIDS, Boston, MA 02115, USA.


The host restriction factor TRIM5alpha mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5alpha variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5alpha B30.2 domain. Human and New World monkey TRIM5alpha 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 TRIM5alpha 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, TRIM5alpha restricts retroviral infection by specifically recognizing the capsid and promoting its rapid, premature disassembly.

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