Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor
- Matthew Stremlau*,†,
- Michel Perron*,†,
- Mark Lee*,
- Yuan Li*,
- Byeongwoon Song*,
- Hassan Javanbakht*,
- Felipe Diaz-Griffero*,
- Donovan J. Anderson‡,
- Wesley I. Sundquist‡, and
- Joseph Sodroski*,§,¶
- *Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Harvard Medical School Division of AIDS, Boston, MA 02115;
- §Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115; and
- ‡Department of Biochemistry, University of Utah, Salt Lake City, UT 84132
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Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved January 19, 2006
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↵ †M.S. and M.P. contributed equally to this work. (received for review November 22, 2005)
Abstract
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.
Footnotes
- ¶To whom correspondence should be addressed. E-mail: joseph_sodroski{at}dfci.harvard.edu
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See Commentary on page 5249.
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Author contributions: M.S., M.P., M.L., Y.L., B.S., W.I.S., and J.S. designed research; M.S., M.P., M.L., Y.L., and B.S. performed research; M.S., M.P., M.L., Y.L., H.J., F.D.-G., D.J.A., and W.I.S. contributed new reagents/analytic tools; M.S., M.P., M.L., Y.L., B.S., W.I.S., and J.S. analyzed data; and M.S. and J.S. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- CA–NC,
- capsid–nucleocapsid;
- HIV-1(Env−),
- control HIV-1 virions without envelope glycoproteins;
- HIV-1(VSV-G),
- vesicular stomatitis virus-G-pseudotyped HIV-1;
- MLV,
- murine leukemia virus;
- N-MLV,
- N-tropic MLV;
- RBCC,
- RING, B-box and coiled-coil;
- VSV,
- vesicular stomatitis virus.
Abbreviations:
- © 2006 by The National Academy of Sciences of the USA
