Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor

M Stremlau, M Perron, M Lee, Y Li… - Proceedings of the …, 2006 - National Acad Sciences
M Stremlau, M Perron, M Lee, Y Li, B Song, H Javanbakht, F Diaz-Griffero, DJ Anderson…
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus
infection; susceptibility to these blocks is determined by viral capsid sequences. Here we
demonstrate that TRIM5α variants from Old World monkeys specifically associate with the
HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5α B30. 2 domain.
Human and New World monkey TRIM5α proteins associated less efficiently with the HIV-1
capsid, accounting for the lack of restriction in cells of these species. After infection, the …
The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5α variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5α B30.2 domain. Human and New World monkey TRIM5α 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 TRIM5α 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, TRIM5α restricts retroviral infection by specifically recognizing the capsid and promoting its rapid, premature disassembly.
National Acad Sciences