title: Small ruminant lentiviral Vif proteins commonly utilize cyclophilin A, an evolutionarily and structurally conserved protein, to degrade ovine and caprine APOBEC3 proteins.
abstract: Mammals have co-evolved with retroviruses, including lentiviruses, over a long period. Evidence supporting this contention is that viral infectivity factor (Vif) encoded by lentiviruses antagonizes the anti-viral action of cellular apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) of the host. To orchestrate E3 ubiquitin ligase complex for APOBEC3 degradation, Vifs utilize mammalian proteins such as core-binding factor beta (CBFB; for primate lentiviruses) or cyclophilin A (CYPA; for Maedi-Visna virus [MVV]). However, the co-evolutionary relationship between lentiviral Vif and the mammalian proteins associated with Vif-mediated APOBEC3 degradation is poorly understood. Moreover, it is unclear whether Vif proteins of small ruminant lentiviruses (SRLVs), including MVV and caprine arthritis encephalitis virus (CAEV), commonly utilize CYPA to degrade the APOBEC3 of their hosts. In this study, molecular phylogenetic and protein homology modeling revealed that Vif co-factors are evolutionarily and structurally conserved. It was also found that not only MVV but also CAEV Vifs degrade APOBEC3 of both sheep and goats and that CAEV Vifs interact with CYPA. These findings suggest that lentiviral Vifs chose evolutionarily and structurally stable proteins as their partners (e.g., CBFB or CYPA) for APOBEC3 degradation and, particularly, that SRLV Vifs evolved to utilize CYPA as their co-factor in degradation of ovine and caprine APOBEC3.
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.
authors.forename: Rokusuke
authors.initials: R
authors.lastname: Yoshikawa
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.|CREST, Japan Science and Technology Agency, Saitama 3220012.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.
authors.forename: Eri
authors.initials: E
authors.lastname: Yamada
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.|Graduate School of Biostudies, Kyoto University, Kyoto 6068501.
authors.forename: Miyu
authors.initials: M
authors.lastname: Moriwaki
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.affiliation: Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 1138510.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, Kanagawa 2430034, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507.|CREST, Japan Science and Technology Agency, Saitama 3220012.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
mesh_terms: D000818:Animals; D016088:Arthritis-Encephalitis Virus, Caprine / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism; D021984:Cyclophilin A / Q000235:genetics* / Q000378:metabolism*; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D016346:Gene Products, vif / Q000235:genetics* / Q000378:metabolism*; D006041:Goats; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D010802:Phylogeny; D012756:Sheep
chemical_list: D050658:Core Binding Factor beta Subunit; D016346:Gene Products, vif; D007376:Interleukin-2; C081786:cyclophilin B; D003564:Cytidine Deaminase; D021984:Cyclophilin A; D021983:Cyclophilins
keywords: APOBEC3; Vif; evolutionary arms race; small ruminant lentivirus