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The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif

Nature Medicine volume 9, pages 1404–1407 (2003)Cite this article

Abstract

The human protein apolipoprotein B mRNA-editing enzyme–catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamination takes place after virus entry into target cells, APOBEC3G function is dependent on its association with the viral nucleoprotein complexes that synthesize cDNA and must therefore be incorporated into virions as they assemble in infected cells. Here we show that the HIV-1 virion infectivity factor (Vif) protein protects the virus from APOBEC3G-mediated inactivation by preventing its incorporation into progeny virions, thus allowing the ensuing infection to proceed without DNA deamination. In addition to helping exclude APOBEC3G from nascent virions, Vif also removes APOBEC3G from virus-producing cells by inducing its ubiquitination and subsequent degradation by the proteasome. Our findings indicate that pharmacologic strategies aimed at stabilizing APOBEC3G in HIV-1 infected cells should be explored as potential HIV/AIDS therapeutics.

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Figure 1: Vif inhibits APOBEC3G packaging into HIV-1 virions.
Figure 2: Vif induces the ubiquitination and proteasomal degradation of APOBEC3G.
Figure 3: Residues in Vif essential for regulating HIV-1 infectivity are required for APOBEC3G degradation.

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Acknowledgements

We thank R. Kopito for the kind gift of ubiquitin expression vectors. This work was supported by Research Grants from the UK Medical Research Council (M.H.M.), the Royal Society (A.M.S.) and the National Science Foundation (N.C.G.). M.H.M. is an Elizabeth Glaser Scientist supported by the Elizabeth Glaser Pediatric AIDS Foundation.

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

    Ann M Sheehy & Michael H Malim

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

    Nathan C Gaddis

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  1. Ann M Sheehy
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Correspondence to Michael H Malim.

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Sheehy, A., Gaddis, N. & Malim, M. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 9, 1404–1407 (2003). https://doi.org/10.1038/nm945

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