The Vif protein of HIV triggers degradation of the human antiretroviral DNA deaminase APOBEC3G.
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. HIV, however, encodes a protein (virion infectivity factor, Vif ), 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.
Conticello
Silvestro G
SG
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. silvoc@mrc-lmb.cam.ac.uk
Harris
Reuben S
RS
Neuberger
Michael S
MS
D000071480:APOBEC-3G Deaminase; D002874:Chromosome Mapping; D003564:Cytidine Deaminase; D017931:DNA Primers; D004586:Electrophoresis; D005434:Flow Cytometry; D016346:Gene Products, vif / Q000378:metabolism*; D006678:HIV / Q000201:enzymology*; D006801:Humans; D015151:Immunoblotting; D009700:Nucleoside Deaminases; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D016346:Gene Products, vif; D011506:Proteins; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase