title: Identification of a Cullin5-ElonginB-ElonginC E3 complex in degradation of feline immunodeficiency virus Vif-mediated feline APOBEC3 proteins.
abstract: Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against a wide range of viruses, such as feline immunodeficiency virus (FIV), feline foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other species. This activity can be counteracted by the FIV Vif protein, but the mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we demonstrated that FIV Vif could act via a proteasome-dependent pathway to overcome fA3s. FIV Vif interacted with feline cellular proteins Cullin5 (Cul5), ElonginB, and ElonginC to form an E3 complex to induce degradation of fA3s. Both the dominant-negative Cul5 mutant and a C-terminal hydrophilic replacement ElonginC mutant potently disrupted the FIV Vif activity against fA3s. Furthermore, we identified a BC-box motif in FIV Vif that was essential for the recruitment of E3 ubiquitin ligase and also required for FIV Vif-mediated degradation of fA3s. Moreover, despite the lack of either a Cul5-box or a HCCH zinc-binding motif, FIV Vif specifically selected Cul5. Therefore, FIV Vif may interact with Cul5 via a novel mechanism. These finding imply that SOCS proteins may possess distinct mechanisms to bind Cul5 during formation of the Elongin-Cullin-SOCS box complex.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, Jilin Province 130012, People's Republic of China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Wang
authors.forename: Wenyan
authors.initials: W
authors.lastname: Zhang
authors.forename: Mingyu
authors.initials: M
authors.lastname: Lv
authors.forename: Tao
authors.initials: T
authors.lastname: Zuo
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
mesh_terms: D000071478:APOBEC Deaminases; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002415:Cats; D002478:Cells, Cultured; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000075065:Elongin; D016181:Feline Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D044842:Cullin Proteins; D000075065:Elongin; D016346:Gene Products, vif; D012333:RNA, Messenger; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase