Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity.
Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G), a cytidine deaminase, is a recently recognized innate intracellular protein with lethal activity against human immunodeficiency virus (HIV). Packaged into progeny virions, APOBEC3G enzymatic activity leads to HIV DNA degradation. As a counterattack, HIV virion infectivity factor (Vif) targets APOBEC3G for proteasomal proteolysis to exclude it from budding virions. Based on the ability of APOBEC3G to antagonize HIV infection, considerable interest hinges on elucidating its mechanism(s) of regulation. In this study, we provide the first evidence that an innate, endogenous host defense factor has the potential to promote APOBEC3G and rebuke the virus-mediated attempt to control its cellular host. We identify interferon (IFN)-alpha as a potent inducer of APOBEC3G to override HIV Vif neutralization of APOBEC3 proteins that pose a threat to efficient macrophage HIV replication. Our data provide a new dimension by which IFN-alpha mediates its antiviral activity and suggest a means to render the host nonpermissive for viral replication.
Peng
Gang
G
Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Lei
Ke Jian
KJ
Jin
Wenwen
W
Greenwell-Wild
Teresa
T
Wahl
Sharon M
SM
D000071480:APOBEC-3G Deaminase; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003564:Cytidine Deaminase; D015870:Gene Expression; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D019380:Anti-HIV Agents; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D007371:Interferon-gamma; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase