Functional domains of APOBEC3G required for antiviral activity.
The viral protein, Vif, is essential for the production of infectious progeny virions in natural target cells of human immunodeficiency virus type 1 (HIV-1). Several recent reports indicate that Vif acts by antagonizing the activity of an endogenous human antiviral protein, APOBEC3G. To investigate this route to restrict HIV-1 infection, we employed mutagenesis to assess APOBEC3G function during HIV-1 infection including interaction with Vif, localization, and activity in virions. We found that APOBEC3G binds Vif in infected cells and the C'-terminal region is required for this interaction. APOBEC3G was only incorporated into virions in the absence of Vif and deletion of either the N'-terminal or C'-terminal regions of APOBEC3G abrogated virion localization. Assaying endogenous reverse transcription we found that APOBEC3G and its C'-terminal deletion mutant inhibited full-length cDNA synthesis, possibly through binding to viral RNA, a function revealed through gel-shift assays. Taken together, our studies suggest that APOBEC3G inhibits HIV-1 infection through interference with reverse transcription and that Vif counteracts APOBEC3G by impeding its entry into virions.
Li
Jinliang
J
Molecular Virology Division, St Luke's-Roosevelt Hospital Center and Columbia University, New York, New York 10019, USA.
Potash
Mary Jane
MJ
Volsky
David J
DJ
D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase; D024202:Electrophoretic Mobility Shift Assay; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation; D009700:Nucleoside Deaminases; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D048348:Reverse Transcription; D014771:Virion / Q000737:chemistry / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D011506:Proteins; D012367:RNA, Viral; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase