title: N-terminal hemagglutinin tag renders lysine-deficient APOBEC3G resistant to HIV-1 Vif-induced degradation by reduced polyubiquitination.
abstract: APOBEC3G, a potent HIV-1 host restriction factor, is overcome by HIV-1 viral infectivity factor (Vif), which induces its polyubiquitination and proteasomal degradation. Here we show that lysine-deficient APOBEC3G with an N-terminal hemagglutinin (HA) tag fusion (HA-A3G20K/R) was resistant to HIV-1 Vif-induced proteasomal degradation. HA-A3G20K/R molecules were packaged into wild-type HIV-1 particles, and HA-A3G20K/R drastically decreased wild-type HIV-1 reverse transcription products and infectivity. We also showed that the N terminus of A3G was a target of polyubiquitination induced by HIV-1 Vif. Thus, fusion of the HA tag to the N terminus of A3G20K/R reduced its polyubiquitination, the likely mechanism for the resistance of this protein to HIV-1 Vif-induced proteasomal degradation. Finding such ways to induce resistance of A3G to Vif may provide new approaches to anti-HIV/AIDS therapy.
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee 37208, USA.
authors.forename: Yudi
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiujia
authors.initials: Q
authors.lastname: Shao
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: James E K
authors.initials: JE
authors.lastname: Hildreth
authors.forename: Bindong
authors.initials: B
authors.lastname: Liu
mesh_terms: D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics*; D025821:Polyubiquitin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D006388:Hemagglutinins; D011993:Recombinant Fusion Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D025821:Polyubiquitin; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D008239:Lysine