title: HIV-1 Vif promotes the formation of high molecular mass APOBEC3G complexes.
abstract: HIV-1 Vif inhibits the antiviral activity of APOBEC3G (APO3G) by inducing proteasomal degradation. Here, we studied the effects of Vif on APO3G in vitro. In this system, Vif did not cause APO3G degradation. Instead, Vif induced changes in APO3G that affected immunoprecipitation of the native protein. This effect required wt Vif and was reversed by heat denaturation of APO3G. Sucrose gradient analysis demonstrated that wt Vif induced the gradual transition of APO3G translated in vitro or expressed in HeLa cells from a low molecular mass conformation to puromycin-sensitive high molecular mass (HMM) complexes. In the absence of Vif or the presence of biologically inactive Vif APO3G failed to form HMM complexes. Our results expose a novel function of Vif that promotes the assembly of APO3G into presumably packaging-incompetent HMM complexes and may explain how Vif can overcome the APO3G-imposed block to HIV replication under conditions of no or inefficient APO3G degradation.
authors.affiliation: Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0460, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Goila-Gaur
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Khan
authors.forename: Eri
authors.initials: E
authors.lastname: Miyagi
authors.forename: Sandra
authors.initials: S
authors.lastname: Kao
authors.forename: Sandrine
authors.initials: S
authors.lastname: Opi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebel
mesh_terms: D000071480:APOBEC-3G Deaminase; D002499:Centrifugation, Density Gradient; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D009154:Mutation; D014176:Protein Biosynthesis; D011489:Protein Denaturation; D014158:Transcription, Genetic; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D054320:vif Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase