Host cell barriers to the early phase of immunodeficiency virus replication explain the current distribution of these viruses among human and non-human primate species1,2,3,4. Human immunodeficiency virus type 1 (HIV-1), the cause of acquired immunodeficiency syndrome (AIDS) in humans, efficiently enters the cells of Old World monkeys but encounters a block before reverse transcription2,3,4. This species-specific restriction acts on the incoming HIV-1 capsid5,6,7 and is mediated by a dominant repressive factor7,8,9. Here we identify TRIM5α, a component of cytoplasmic bodies, as the blocking factor. HIV-1 infection is restricted more efficiently by rhesus monkey TRIM5α than by human TRIM5α. The simian immunodeficiency virus, which naturally infects Old World monkeys10, is less susceptible to the TRIM5α-mediated block than is HIV-1, and this difference in susceptibility is due to the viral capsid. The early block to HIV-1 infection in monkey cells is relieved by interference with TRIM5α expression. Our studies identify TRIM5α as a species-specific mediator of innate cellular resistance to HIV-1 and reveal host cell components that modulate the uncoating of a retroviral capsid.
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We thank S. Farnum and Y. McLaughlin for manuscript preparation; and S. Basmaciogullari, R. Lu, N. Vandegraaff and A. Engelman for advice and reagents. This work was supported by grants from the NIH, by a Center for AIDS Research Award, by the International AIDS Vaccine Initiative, and by the Bristol-Myers Squibb Foundation. M.S. is supported by a National Defense Science and Engineering Fellowship and is a Fellow of the Ryan Foundation.
The authors declare that they have no competing financial interests.
TRIM5αrh restricts infectious HIV-1 replication at an increased multiplicity of infection. (PDF 50 kb)
Effects of the HA tag on the ability of human and rhesus TRIM5α to restrict virus infection. (PDF 64 kb)
Interference with TRIM5αrh expression in rhesus kidney cells relieves the post-entry restriction to HIV-1. (PDF 79 kb)
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Stremlau, M., Owens, C., Perron, M. et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427, 848–853 (2004) doi:10.1038/nature02343
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