Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor.
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.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School Division of AIDS, Boston, MA 02115, USA.
Matthew
M
Stremlau
Michel
M
Perron
Mark
M
Lee
Yuan
Y
Li
Byeongwoon
B
Song
Hassan
H
Javanbakht
Felipe
F
Diaz-Griffero
Donovan J
DJ
Anderson
Wesley I
WI
Sundquist
Joseph
J
Sodroski
D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003600:Cytosol / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D013045:Species Specificity; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases