The Vif Protein of HIV Triggers Degradation of the Human Antiretroviral DNA Deaminase APOBEC3G

Silvestro G. Conticello, Reuben S. Harris, Michael S. Neuberger

Research output: Contribution to journalArticlepeer-review

387 Scopus citations

Abstract

APOBEC3G is a human cellular enzyme that is incorporated into retroviral particles and acts to restrict retroviral replication in infected cells by deaminating dC to dU in the first (minus)-strand cDNA replication intermediate [1-5]. HIV, however, encodes a protein (virion infectivity factor, Vif [6, 7]), which overcomes APOBEC3G-mediated restriction but by an unknown mechanism. Here, we show that Vif triggers APOBEC3G degradation by a proteasome-dependent pathway and that an 80 amino acid region of APOBEC3G surrounding its first zinc coordination motif is sufficient to confer the ability to partake in an interaction involving Vif. Inhibitors of this interaction might therefore prove therapeutically useful in blocking Vif-mediated APOBEC3G destruction.

Original languageEnglish (US)
Pages (from-to)2009-2013
Number of pages5
JournalCurrent Biology
Volume13
Issue number22
DOIs
StatePublished - Nov 11 2003

Bibliographical note

Funding Information:
We thank R. Grenfell for assistance with flow cytometry; the Centralised Facility for AIDS Reagents for monoclonal anti-Vif antibodies; J. Sale for the ubiquitin-encoding plasmid; and M. Malim for the Vif-encoding plasmids as well as communicating unpublished results. We thank C. Rada, S.K. Petersen-Mahrt, S. Munro, and H. Pelham for the helpful discussions. S.G.C. was supported by a Marie Curie Fellowship of the European Community program FP5 under contract number MCFI-2002-01357, R.S.H. by a Burroughs Wellcome Fund Hitchings-Elion fellowship, and the work was also in part supported by a grant from the Leukaemia Research Fund to R.S.H. and M.S.N.

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