APOBEC3G is incorporated into virus-like particles by a direct interaction with HIV-1 Gag nucleocapsid protein.
APOBEC3G belongs to the family of cellular cytidine deaminase-editing enzymes with a potent antiretroviral activity, which is counteracted by the Vif protein expressed by lentiviruses. Antiretroviral activity of APOBEC3G requires its packaging into assembling virions, presumably to ensure its close association with nascent retroviral cDNA. Here, we demonstrate that APOBEC3G is encapsidated through a direct interaction with the HIV-1 Gag polyprotein which likely takes place on the membranes of the multivesicular bodies (MVB)/late endosomal compartments. This interaction is mediated by the Gag nucleocapsid protein NC, and the N-terminal part of NC is most critical for this interaction. Binding to the NC domain would ensure that APOBEC3G will be concentrated in the viral core of mature HIV-1, in close proximity to the reverse transcription complex.
Alce
Timothy M
TM
Oncology Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA.
Popik
Waldemar
W
D000071480:APOBEC-3G Deaminase; D044966:Anti-Retroviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D003564:Cytidine Deaminase; D018076:DNA, Complementary / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism*; D016346:Gene Products, vif / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008055:Lipids / Q000737:chemistry; D021962:Membrane Microdomains; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D019251:Nucleocapsid / Q000378:metabolism; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D009700:Nucleoside Deaminases; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins; D012190:Retroviridae / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D019065:Virus Assembly; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D044966:Anti-Retroviral Agents; D018076:DNA, Complementary; D015683:Gene Products, gag; D016346:Gene Products, vif; D008055:Lipids; D019590:Nucleocapsid Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D012313:RNA; D005982:Glutathione Transferase; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase