Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif.
The HIV-1 accessory protein Vif (virion infectivity factor) is required for the production of infectious virions by CD4(+) lymphocytes. Vif facilitates particle infectivity by blocking the inhibitory activity of APOBEC3G (CEM15), a virion-encapsidated cellular protein that deaminates minus-strand reverse transcript cytosines to uracils. We report that HIV-1 Vif forms a complex with human APOBEC3G that prevents its virion encapsidation. HIV-1 Vif did not efficiently form a complex with mouse APOBEC3G. Vif dramatically reduced the amount of human APOBEC3G encapsidated in HIV-1 virions but did not prevent encapsidation of mouse or AGM APOBEC3G. As a result, these enzymes are potent inhibitors of wild-type HIV-1 replication. The species-specificity of this interaction may play a role in restricting HIV-1 infection to humans. Together these findings suggest that therapeutic intervention that either induced APOBEC3G or blocked its interaction with Vif could be clinically beneficial.
Mariani
Roberto
R
Infectious Disease Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chen
Darlene
D
Schröfelbauer
Bärbel
B
Navarro
Francisco
F
König
Renate
R
Bollman
Brooke
B
Münk
Carsten
C
Nymark-McMahon
Henrietta
H
Landau
Nathaniel R
NR
D000071480:APOBEC-3G Deaminase; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002213:Capsid / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D003564:Cytidine Deaminase; D018076:DNA, Complementary / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D016346:Gene Products, vif / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology* / Q000821:virology*; D015497:HIV-1 / Q000201:enzymology* / Q000472:pathogenicity; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009700:Nucleoside Deaminases; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D013045:Species Specificity; D014158:Transcription, Genetic / Q000235:genetics; D014771:Virion / Q000201:enzymology*; D014779:Virus Replication / Q000502:physiology*; D054320:vif Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D018076:DNA, Complementary; D016346:Gene Products, vif; D046911:Macromolecular Substances; 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