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HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation

Nature Medicine volume 9, pages 1398–1403 (2003)Cite this article

Abstract

The viral infectivity factor (Vif) encoded by HIV-1 neutralizes a potent antiviral pathway that occurs in human T lymphocytes and several leukemic T-cell lines termed nonpermissive, but not in other cells termed permissive. In the absence of Vif, this antiviral pathway efficiently inactivates HIV-1. It was recently reported that APOBEC3G (also known as CEM-15), a cytidine deaminase nucleic acid–editing enzyme, confers this antiviral phenotype on permissive cells. Here we describe evidence that Vif binds APOBEC3G and induces its rapid degradation, thus eliminating it from cells and preventing its incorporation into HIV-1 virions. Studies of Vif mutants imply that it contains two domains, one that binds APOBEC3G and another with a conserved SLQ(Y/F)LA motif that mediates APOBEC3G degradation by a proteasome-dependent pathway. These results provide promising approaches for drug discovery.

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Figure 1: Expression of Vif downmodulates APOBEC3G-Myc in 293T cells.
Figure 2: Effects of Vif on APOBEC3G-Myc.
Figure 3: Vif prevents viral encapsidation of APOBEC3G-Myc.
Figure 4: Vif binds to APOBEC3G-Myc.
Figure 5: Vif causes rapid degradation of APOBEC3G-Myc.
Figure 6: APOBEC3G-Myc degradation by Vif involves a proteasome-dependent pathway.

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Acknowledgements

This research was supported by National Institutes of Health grant AI49729 to D.K. K.R. was the recipient of a predoctoral fellowship from the Department of Hematology and Oncology at Oregon Health & Science University. We thank D. Gabuzda for providing the pcDNA3.1-Vif vector, M. Malim for the Vif deletion mutants and M. Thayer for the S2 probe.

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  1. Mariana Marin, Kristine M Rose and Susan L Kozak: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L224, Portland, 97239-3098, Oregon, USA

    Mariana Marin, Kristine M Rose, Susan L Kozak & David Kabat

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Correspondence to David Kabat.

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Marin, M., Rose, K., Kozak, S. et al. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med 9, 1398–1403 (2003). https://doi.org/10.1038/nm946

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