title: Comparison of genotypes I and III in Japanese encephalitis virus reveals distinct differences in their genetic and host diversity.
abstract: Japanese encephalitis (JE) is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been phylogenetically divided into five genotypes. Recent surveillance data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. To investigate the mechanism behind the genotype shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination, we collected (i) all full-length and partial JEV molecular sequences and (ii) associated genotype and host information comprising a data set of 873 sequences. We then examined differences between the two genotypes at the genetic and epidemiological level by investigating amino acid mutations, positive selection, and host range. We found that although GI is dominant, it has fewer sites predicted to be under positive selection, a narrower host range, and significantly fewer human isolates. For the E protein, the sites under positive selection define a haplotype set for each genotype that shows striking differences in their composition and diversity, with GIII showing significantly more variety than GI. Our results suggest that GI has displaced GIII by achieving a replication cycle that is more efficient but is also more restricted in its host range.
  
  
  OBJECTIVE
  Japanese encephalitis is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been divided into five genotypes based on sequence similarity. Recent data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. Understanding the reasons behind this shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination is important for controlling the spread of the virus and reducing human fatalities. We collected all available full-length and partial JEV molecular sequences and associated genotype and host information. We then examined differences between the two genotypes at the genetic and epidemiological levels by investigating amino acid mutations, positive selection, and host range. Our results suggest that GI has displaced GIII by achieving a replication cycle that is more efficient but more restricted in host range.
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Na
authors: N
authors: Han
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: James
authors: J
authors: Adams
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Ping
authors: P
authors: Chen
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Zhen-yang
authors: ZY
authors: Guo
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Xiang-fu
authors: XF
authors: Zhong
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Wei
authors: W
authors: Fang
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Na
authors: N
authors: Li
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Lei
authors: L
authors: Wen
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Xiao-yan
authors: XY
authors: Tao
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Zhi-ming
authors: ZM
authors: Yuan
authors: Bioinformatics Group, Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China simon.rayner.cn@gmail.com.
authors: Simon
authors: S
authors: Rayner
mesh_terms: D000818:Animals; D001208:Asia / Q000453:epidemiology; D002519:Ceratopogonidae; D002685:Chiroptera; D009033:Culicidae / Q000821:virology*; D004197:Disease Reservoirs; D004664:Encephalitis Virus, Japanese / Q000145:classification / Q000235:genetics*; D004672:Encephalitis, Japanese / Q000453:epidemiology* / Q000821:virology; D005838:Genotype; D006736:Horses; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D007303:Insect Vectors / Q000821:virology*; D008958:Models, Molecular; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012703:Serotyping; D013552:Swine
chemical_list: D012367:RNA, Viral