title: Core-binding factor subunit beta is not required for non-primate lentiviral Vif-mediated APOBEC3 degradation.
abstract: Viral infectivity factor (Vif) is required for lentivirus fitness and pathogenicity, except in equine infectious anemia virus (EIAV). Vif enhances viral infectivity by a Cullin5-Elongin B/C E3 complex to inactivate the host restriction factor APOBEC3. Core-binding factor subunit beta (CBF-β) is a cell factor that was recently shown to be important for the primate lentiviral Vif function. Non-primate lentiviral Vif also degrades APOBEC3 through the proteasome pathway. However, it is unclear whether CBF-β is required for the non-primate lentiviral Vif function. In this study, we demonstrated that the Vifs of non-primate lentiviruses, including feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), and maedi-visna virus (MVV), do not interact with CBF-β. In addition, CBF-β did not promote the stability of FIV, BIV, CAEV, and MVV Vifs. Furthermore, CBF-β silencing or overexpression did not affect non-primate lentiviral Vif-mediated APOBEC3 degradation. Our results suggest that non-primate lentiviral Vif induces APOBEC3 degradation through a different mechanism than primate lentiviral Vif. Importance: The APOBEC3 protein family members are host restriction factors that block retrovirus replication. Vif, an accessory protein of lentivirus, degrades APOBEC3 to rescue viral infectivity by forming Cullin5-Elongin B/C-based E3 complex. CBF-β was proved to be a novel regulator of primate lentiviral Vif function. In this study, we found that CBF-β knockdown or overexpression did not affect FIV Vif's function, which induced polyubiquitination and degradation of APOBEC3 by recruiting the E3 complex in a manner similar to that of HIV-1 Vif. We also showed that other non-primate lentiviral Vifs did not require CBF-β to degrade APOBEC3. CBF-β did not interact with non-primate lentiviral Vifs or promote their stability. These results suggest that a different mechanism exists for the Vif-APOBEC interaction and that non-primates are not suitable animal models for exploring pharmacological interventions that disrupt Vif-CBF-β interaction.
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China College of Wildlife Resources, Northeast Forestry University, Harbin, China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Ai
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China College of Wildlife Resources, Northeast Forestry University, Harbin, China.
authors.forename: Dantong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Cuihui
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: College of Wildlife Resources, Northeast Forestry University, Harbin, China jianzhangma@163.com xjw@hvri.ac.cn.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China jianzhangma@163.com xjw@hvri.ac.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
mesh_terms: D000071478:APOBEC Deaminases; D001483:Base Sequence; D050658:Core Binding Factor beta Subunit / Q000502:physiology*; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000378:metabolism*; D017931:DNA Primers; D016346:Gene Products, vif / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000145:classification / Q000502:physiology*; D059748:Proteolysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C493692:CBFB protein, human; D050658:Core Binding Factor beta Subunit; D017931:DNA Primers; D016346:Gene Products, vif; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase