title: Genetic Evolution during the development of an attenuated EIAV vaccine.
abstract: BACKGROUND
  The equine infectious anemia virus (EIAV) vaccine is the only attenuated lentiviral vaccine applied on a large scale that has been shown to be effective in controlling the prevalence of EIA in China. This vaccine was developed by successive passaging of a field-isolated virulent strain in different hosts and cultivated cells. To explore the molecular basis for the phenotype alteration of this vaccine strain, we systematically analyzed its genomic evolution during vaccine development.
  
  
  RESULTS
  Sequence analysis revealed that the genetic distance between the wild-type strain and six representative strains isolated from key development stages gradually increased with the number of passages. Env gene, but not gag and pol, showed a clear evolutionary flow similar to that of the whole genomes of different generations during the attenuation. Stable mutations were identified in multiple regions of multiple genes along with virus passaging. The adaption of the virus to the growth environment of cultured cells with accumulated genomic and genetic variations was positively correlated with the reduction in pathogenicity and rise of immunogenicity. Statistical analyses revealed significant differences in the frequency of the most stable mutations between in vivo and ex vivo-adapted strains and between virulent and attenuated strains.
  
  
  CONCLUSIONS
  These data indicate that EIAV evolution during vaccine development generated an accumulation of mutations under the selective drive force, which helps to better understand the molecular basis of lentivirus pathogenicity and immunogenicity.
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. xuefengwang1982@126.com.|Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. xuefengwang1982@126.com.
authors: Xue-Feng
authors: XF
authors: Wang
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. sndhr@163.com.
authors: Yue-Zhi
authors: YZ
authors: Lin
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. liqiang007200@sina.com.|Harbin Weike Biotechnology Development Company, Harbin, China. liqiang007200@sina.com.
authors: Qiang
authors: Q
authors: Li
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. liuqiang_yyy@163.com.
authors: Qiang
authors: Q
authors: Liu
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. vivilnic@163.com.
authors: Wei-Wei
authors: WW
authors: Zhao
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. chengdu1981@163.com.
authors: Cheng
authors: C
authors: Du
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. 18047113976@163.com.
authors: Jie
authors: J
authors: Chen
authors: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. xjw@hvri.ac.cn.
authors: Xiaojun
authors: X
authors: Wang
authors: 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 Co., Harbin, 150069, China. jianhua_uc@126.com.
authors: Jian-Hua
authors: JH
authors: Zhou
mesh_terms: D000818:Animals; D002681:China; D018397:Equidae; D004859:Equine Infectious Anemia / Q000517:prevention & control*; D019143:Evolution, Molecular; D006736:Horses; D004860:Infectious Anemia Virus, Equine / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D014613:Vaccines, Attenuated; D014765:Viral Vaccines