title: Phylodynamic analysis of the canine distemper virus hemagglutinin gene.
abstract: BACKGROUND
  Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV. A total of 188 full-length CDV hemagglutinin (H) gene sequences dataset were subjected to recombination analysis, including seven from modified live vaccine (MLV) strains and 12 from Taiwan specimens. After excluding the MLV strains and potential recombinant strains, alignments of 176 of 188 previous CDV strains were further used to analyze phylodynamic characteristics, and evidence of selection, and co-evolution.
  
  
  RESULTS
  The CDV genotype consisted of MLV-associated genotypes such as America-1 and Rockborn-like strains, which were characterized by long terminal branches and no distinct geographical patterns among lineages. In contrast, wild-type isolates clustered into lineages with a spatiotemporal structure and short terminal branches. Co-circulation and extensive diversification were simultaneously observed. The sequence variation signature was shaped by both geographic diversity and host tropism. Codon 506 was identified as a multi-epistatic interacting in the H protein.
  
  
  CONCLUSIONS
  The topological signature revealed in this study suggests different epidemic scenarios. For example, a ladder-like backbone is a hallmark of directional selection, and cladogenesis at long terminal branches indicates the emergence of a surviving lineage. The stable effective viral population of CDV indicate the effectiveness of vaccines currently used to control the virus.
authors.affiliation: Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan. mirage-ke@yahoo.com.tw.
authors.forename: Guan-Ming
authors.initials: GM
authors.lastname: Ke
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan. ace58606138@yahoo.com.tw.
authors.forename: Chin-Hsiang
authors.initials: CH
authors.lastname: Ho
authors.affiliation: Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan. s75812@yahoo.com.tw.|Country Year Limited Company, Taoyuan, Taiwan. s75812@yahoo.com.tw.
authors.forename: Meng-Jung
authors.initials: MJ
authors.lastname: Chiang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. nenneht@gmail.com.|Department of laboratory medicine, Edward Francis Small Teaching Hospital, Banjul, Gambia. nenneht@gmail.com.
authors.forename: Bintou
authors.initials: B
authors.lastname: Sanno-Duanda
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan. cschung@mail.npust.edu.tw.
authors.forename: Cheng-Shu
authors.initials: CS
authors.lastname: Chung
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan. mylin@mail.npust.edu.tw.
authors.forename: Maw-Yeong
authors.initials: MY
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. wing_282@hotmail.com.
authors.forename: Yong-Ying
authors.initials: YY
authors.lastname: Shi
authors.affiliation: Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. w3e3@hotmail.com.|Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. w3e3@hotmail.com.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. yctyan@kmu.edu.tw.|Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. yctyan@kmu.edu.tw.
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Tyan
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan. liaopc@mail.ncku.edu.tw.
authors.forename: Pao-Chi
authors.initials: PC
authors.lastname: Liao
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. peiyuchu@kmu.edu.tw.|Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. peiyuchu@kmu.edu.tw.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chu
mesh_terms: D000818:Animals; D004216:Distemper / Q000821:virology*; D004217:Distemper Virus, Canine; D004285:Dogs; D005260:Female; D015967:Gene Expression Regulation, Viral; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010802:Phylogeny
chemical_list: D006388:Hemagglutinins