TY - JOUR
T1 - Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor
AU - Stremlau, Matthew
AU - Perron, Michel
AU - Lee, Mark
AU - Li, Yuan
AU - Song, Byeongwoon
AU - Javanbakht, Hassan
AU - Diaz-Griffero, Felipe
AU - Anderson, Donovan J.
AU - Sundquist, Wesley I.
AU - Sodroski, Joseph
PY - 2006/4/4
Y1 - 2006/4/4
N2 - 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.
AB - 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.
KW - B30.2(SPRY) domain
KW - HIV-1
KW - Innate immunity
KW - RING, B-box, and coiled-coil protein
KW - Tripartite motif
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U2 - 10.1073/pnas.0509996103
DO - 10.1073/pnas.0509996103
M3 - Article
C2 - 16540544
AN - SCOPUS:33645794537
SN - 0027-8424
VL - 103
SP - 5514
EP - 5519
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -
