title: Role of cullin-elonginB-elonginC E3 complex in bovine immunodeficiency virus and maedi-visna virus Vif-mediated degradation of host A3Z2-Z3 proteins.
abstract: BACKGROUND
  All lentiviruses except equine infectious anemia virus (EIVA) antagonize antiviral family APOBEC3 (A3) proteins of the host through viral Vif proteins. The mechanism by which Vif of human, simian or feline immunodeficiency viruses (HIV/SIV/FIV) suppresses the corresponding host A3s has been studied extensively.
  
  
  RESULTS
  Here, we determined that bovine immunodeficiency virus (BIV) and maedi-visna virus (MVV) Vif proteins utilize the Cullin (Cul)-ElonginB (EloB)-ElonginC (EloC) complex (BIV Vif recruits Cul2, while MVV Vif recruits Cul5) to degrade Bos taurus (bt)A3Z2-Z3 and Ovis aries (oa)A3Z2-Z3, respectively, via a proteasome-dependent but a CBF-β-independent pathway. Mutation of the BC box in BIV and MVV Vif, C-terminal hydrophilic replacement of btEloC and oaEloC and dominant-negative mutants of btCul2 and oaCul5 could disrupt the activity of BIV and MVV Vif, respectively. While the membrane-permeable zinc chelator TPEN could block BIV Vif-mediated degradation of btA3Z2-Z3, it had minimal effects on oaA3Z2-Z3 degradation induced by MVV Vif, indicating that Zn is important for the activity of BIV Vif but not MVV Vif. Furthermore, we identified a previously unreported zinc binding loop [C-x1-C-x1-H-x19-C] in the BIV Vif upstream BC box which is critical for its degradation activity.
  
  
  CONCLUSIONS
  A novel zinc binding loop was identified in the BIV Vif protein that is important for the E3 ubiquination activity, suggesting that the degradation of btA3Z2-Z3 by BIV and that of oaA3Z2-Z3 by MVV Vif may need host factors other than CBF-β.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Wu
authors.forename: Weiran
authors.initials: W
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Jiawen
authors.initials: J
authors.lastname: Wang
authors.forename: Mingyu
authors.initials: M
authors.lastname: Lv
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D044842:Cullin Proteins / Q000502:physiology*; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000378:metabolism*; D000075065:Elongin; D016346:Gene Products, vif / Q000737:chemistry / Q000502:physiology*; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016087:Immunodeficiency Virus, Bovine / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D014790:Visna-maedi virus / Q000502:physiology*
chemical_list: D044842:Cullin Proteins; C000616396:ELOB protein, human; C000616395:ELOC protein, human; D000075065:Elongin; D016346:Gene Products, vif; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase