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

Nature volume 427, pages 848–853 (2004)Cite this article

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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Authors and Affiliations

  1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Matthew Stremlau, Christopher M. Owens, Michel J. Perron, Michael Kiessling & Joseph Sodroski

  2. Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Department of Medicine, Division of AIDS, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Patrick Autissier

  3. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Massachusetts, 02115, Boston, USA

    Joseph Sodroski

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Correspondence to Joseph Sodroski.

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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)

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). https://doi.org/10.1038/nature02343

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