The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys

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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Figure 1: Rhesus monkey TRIM5αrh preferentially blocks HIV-1 infection.
Figure 2: TRIM5αrh blocks HIV-1 infection before or during early reverse transcription.
Figure 3: HIV-1 infection is blocked less efficiently by TRIM5 variants than by TRIM5αrh.
Figure 4: TRIM5αrh is essential for the block to HIV-1 infection in PRL cells.

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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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Correspondence to Joseph Sodroski.

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The authors declare that they have no competing financial interests.

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)

Supplementary Figure Legends (DOC 21 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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