Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity of a degradation-resistant APOBEC3G variant.
Human immunodeficiency virus type 1 (HIV-1) Vif counteracts the antiviral activity of the human cytidine deaminase APOBEC3G (APO3G) by inhibiting its incorporation into virions. This has been attributed to the Vif-induced degradation of APO3G by cytoplasmic proteasomes. We recently demonstrated that although APO3G has a natural tendency to form RNA-dependent homo-multimers, multimerization was not essential for encapsidation into HIV-1 virions or antiviral activity. We now demonstrate that a multimerization-defective APO3G variant (APO3G C97A) is able to assemble into RNase-sensitive high-molecular-mass (HMM) complexes, suggesting that homo-multimerization of APO3G and assembly into HMM complexes are unrelated RNA-dependent processes. Interestingly, APO3G C97A was highly resistant to Vif-induced degradation even though the two proteins were found to interact in coimmunoprecipitation experiments and exhibited partial colocalization in transfected HeLa cells. Surprisingly, encapsidation and antiviral activity of APO3G C97A were both inhibited by Vif despite resistance to degradation. These results demonstrate that targeting of APO3G to proteasome degradation and interference with viral encapsidation are distinct functional properties of Vif.
Opi
Sandrine
S
Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 310, 4 Center Drive, MSC 0460, Bethesda, Maryland 20892-0460, USA.
Kao
Sandra
S
Goila-Gaur
Ritu
R
Khan
Mohammad A
MA
Miyagi
Eri
E
Takeuchi
Hiroaki
H
Strebel
Klaus
K
D000071480:APOBEC-3G Deaminase; D000818:Animals; D003564:Cytidine Deaminase; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009700:Nucleoside Deaminases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D020033:Protein Isoforms; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D046988:Proteasome Endopeptidase Complex; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase