TY - JOUR
T1 - The Vif Protein of HIV Triggers Degradation of the Human Antiretroviral DNA Deaminase APOBEC3G
AU - Conticello, Silvestro G.
AU - Harris, Reuben S.
AU - Neuberger, Michael S.
N1 - 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J. Sale for the ubiquitin-encoding plasmid; and M. Malim for the Vif-encoding plasmids as well as communicating unpublished results.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.
PY - 2003/11/11
Y1 - 2003/11/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cub.2003.10.034
DO - 10.1016/j.cub.2003.10.034
M3 - Article
C2 - 14614829
AN - SCOPUS:0242709301
SN - 0960-9822
VL - 13
SP - 2009
EP - 2013
JO - Current Biology
JF - Current Biology
IS - 22
ER -