Abstract
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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Acknowledgements
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.
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Supplementary information
Supplementary Figure 1
TRIM5αrh restricts infectious HIV-1 replication at an increased multiplicity of infection. (PDF 50 kb)
Supplementary Figure 2
Effects of the HA tag on the ability of human and rhesus TRIM5α to restrict virus infection. (PDF 64 kb)
Supplementary Figure 3
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). https://doi.org/10.1038/nature02343
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DOI: https://doi.org/10.1038/nature02343
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