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Nature 418, 646-650 (8 August 2002) | doi:10.1038/nature00939; Received 30 May 2002; Accepted 1 July 2002; Published online 14 July 2002

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

Ann M. Sheehy1, Nathan C. Gaddis1, Jonathan D. Choi2 & Michael H. Malim1,3

  1. Department of Microbiology, The Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
  2. Division of Human Genetics, The Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
  3. Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, King's College London, London SE1 9RT, UK

Correspondence to: Michael H. Malim1,3 Correspondence and requests for materials should be addressed to M.H.M. (e-mail: Email: michael.malim@kcl.ac.uk).

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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.

  1. Department of Microbiology, The Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
  2. Division of Human Genetics, The Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
  3. Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, King's College London, London SE1 9RT, UK

Correspondence to: Michael H. Malim1,3 Correspondence and requests for materials should be addressed to M.H.M. (e-mail: Email: michael.malim@kcl.ac.uk).