HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation.
The viral infectivity factor (Vif) encoded by HIV-1 neutralizes a potent antiviral pathway that occurs in human T lymphocytes and several leukemic T-cell lines termed nonpermissive, but not in other cells termed permissive. In the absence of Vif, this antiviral pathway efficiently inactivates HIV-1. It was recently reported that APOBEC3G (also known as CEM-15), a cytidine deaminase nucleic acid-editing enzyme, confers this antiviral phenotype on permissive cells. Here we describe evidence that Vif binds APOBEC3G and induces its rapid degradation, thus eliminating it from cells and preventing its incorporation into HIV-1 virions. Studies of Vif mutants imply that it contains two domains, one that binds APOBEC3G and another with a conserved SLQ(Y/F)LA motif that mediates APOBEC3G degradation by a proteasome-dependent pathway. These results provide promising approaches for drug discovery.
Marin
Mariana
M
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L224, Portland, Oregon 97239-3098, USA.
Rose
Kristine M
KM
Kozak
Susan L
SL
Kabat
David
D
D000071480:APOBEC-3G Deaminase; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003564:Cytidine Deaminase; D016346:Gene Products, vif / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006790:Host-Parasite Interactions / Q000502:physiology; D006801:Humans; D009700:Nucleoside Deaminases; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D011506:Proteins; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase