Enzymatically active APOBEC3G is required for efficient inhibition of human immunodeficiency virus type 1.
APOBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. Initial studies of the function of APO3G demonstrated extensive mutation of the viral genome, suggesting a model in which APO3G's antiviral activity is due to hypermutation of the viral genome. Recent studies, however, found that deaminase-defective APO3G mutants transiently expressed in virus-producing cells exhibited significant antiviral activity, suggesting that the antiviral activity of APO3G could be dissociated from its deaminase activity. To directly compare the antiviral activities of wild-type (wt) and deaminase-defective APO3G, we used two approaches: (i) we titrated wt and deaminase-defective APO3G in transient-transfection studies to achieve similar levels of virus-associated APO3G and (ii) we constructed stable cell lines and selected clones expressing comparable amounts of wt and deaminase-defective APO3G. Viruses produced under these conditions were tested for viral infectivity. The results from the two approaches were consistent and suggested that the antiviral activity of deaminase-defective APO3G was significantly lower than that of wt APO3G. We conclude that efficient inhibition of vif-defective human immunodeficiency virus type 1 requires catalytically active APO3G.
Miyagi
Eri
E
Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892-0460, USA.
Opi
Sandrine
S
Takeuchi
Hiroaki
H
Khan
Mohammad
M
Goila-Gaur
Ritu
R
Kao
Sandra
S
Strebel
Klaus
K
D000071480:APOBEC-3G Deaminase; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016341:Genes, vif; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D011817:Rabbits; D014162:Transfection
D000998:Antiviral Agents; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase