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Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein

Nature volume 418, pages 646–650 (2002)Cite this article

Abstract

Viruses have developed diverse non-immune strategies to counteract host-mediated mechanisms that confer resistance to infection. The Vif (virion infectivity factor) proteins are encoded by primate immunodeficiency viruses, most notably human immunodeficiency virus-1 (HIV-1). These proteins are potent regulators of virus infection and replication and are consequently essential for pathogenic infections in vivo1,2,3,4,5,6. HIV-1 Vif seems to be required during the late stages of virus production3,6 for the suppression of an innate antiviral phenotype that resides in human T lymphocytes7,8. Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious. Here, we describe a unique cellular gene, CEM15, whose transient or stable expression in cells that do not normally express CEM15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif. Because the Vif:CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies.

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Figure 1: Replication of HIV-1 in non-permissive and permissive T cells.
Figure 2: Northern analysis of CEM15 expression in non-permissive and permissive cells.
Figure 3: Expression of CEM15 in permissive cells inhibits the infectivity of HIV-1/Δvif.
Figure 4: Stable expression of CEM15 in CEM-SS cells selectively inhibits HIV-1/Δvif replication.
Figure 5: Incorporation of CEM15 into virions.
Figure 6: Amino-acid sequence of CEM15.

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Acknowledgements

We thank D. Gabuzda for the CEM cells. This work was supported by Research Grants from the National Institutes of Health (M.H.M. and A.M.S.), the National Science Foundation (N.C.G.) and the UK Medical Research Council (M.H.M.). M.H.M. is an Elizabeth Glaser Scientist supported by the Elizabeth Glaser Pediatric AIDS Foundation.

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Authors and Affiliations

  1. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA

    Ann M. Sheehy, Nathan C. Gaddis & Michael H. Malim

  2. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA

    Jonathan D. Choi

  3. Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, King's College London, SE1 9RT, London, UK

    Michael H. Malim

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Correspondence to Michael H. Malim.

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Sheehy, A., Gaddis, N., Choi, J. et al. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418, 646–650 (2002). https://doi.org/10.1038/nature00939

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