title: Double-stranded-RNA-specific adenosine deaminase 1 (ADAR1) is proposed to contribute to the adaptation of equine infectious anemia virus from horses to donkeys.
abstract: Equine infectious anemia virus (EIAV) is a member of the genus Lentivirus of the family Retroviridae. Horses are the most susceptible equids to EIAV infection and are therefore the primary hosts of this virus. In contrast, infected donkeys do not develop clinically active equine infectious anemia (EIA). This phenomenon is similar to what has been observed with HIV-1, which fails to induce AIDS in non-human primates. Interestingly, Shen et al. developed a donkey-tropic pathogenic virus strain (EIAVDV117, DV117) by serially passaging a horse-tropic pathogenic strain, EIAVLN40 (LN40), in donkeys. LN40, which was generated by passaging a field isolate in horses, displayed enhanced virulence in horses but caused no clinical symptoms in donkeys. Infection with DV117 induced acute EIA in nearly 100 % of donkeys. Genomic analysis of DV117 revealed a significantly higher frequency of A-to-G substitutions when compared to LN40. Furthermore, detailed analysis of dinucleotide editing showed that A-to-G mutations had a preference for 5'TpA and 5'ApA. These results strongly implicated the activity of the adenosine deaminase, ADAR1, in this type of mutation. Further investigation demonstrated that overexpression of donkey ADAR1 increased A-to-G mutations within the genome of EIAV. Together with our previous finding that multiple mutations in multiple genes are generated in DV117 during its adaptation from horses to donkeys, the present study suggests that ADAR1-induced A-to-G mutations occur during virus adaption to related new hosts contributing to the alteration of EIAV host tropism.
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
authors.forename: Yan-Dong
authors.initials: YD
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Na
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.|Reproductive Medicine Center, Subei People's Hospital of Jiangsu Province (Clinic Medical College of Yang Zhou University), Yangzhou, 225001, China.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. xjw@hvri.ac.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. jianhua_uc@126.com.|Harbin Pharmaceutical Group Biovaccine Company, Harbin, 150069, China. jianhua_uc@126.com.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhou
mesh_terms: D000220:Adaptation, Biological; D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D018397:Equidae; D006736:Horses; D004860:Infectious Anemia Virus, Equine / Q000235:genetics* / Q000472:pathogenicity*; D017354:Point Mutation; D012330:RNA, Double-Stranded / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012692:Serial Passage
chemical_list: D012330:RNA, Double-Stranded; D000243:Adenosine Deaminase