title: Genotype shift in human coronavirus OC43 and emergence of a novel genotype by natural recombination.
abstract: BACKGROUND
  Human coronavirus (HCoV) OC43 is the most prevalent HCoV in respiratory tract infections. Its molecular epidemiological characterization, particularly the genotyping, was poorly addressed.
  
  
  METHODS
  The full-length spike (S), RNA-dependent RNA polymerase (RdRp), and nucleocapsid (N) genes were amplified from each respiratory sample collected from 65 HCoV-OC43-positive patients between 2005 and 2012. Genotypes were determined by phylogenetic analysis. Recombination was analyzed based on full-length viral genome sequences. Clinical manifestations of each HCoV genotype infection were compared by reviewing clinical records.
  
  
  RESULTS
  Sixty of these 65 samples belong to genotypes B, C and D. The remaining five strains had incongruent positions in the phylogenetic trees of the S, RdRp and N genes, suggesting a novel genotype emerging, designated as genotype E. Whole genome sequencing and bootscan analysis indicated that genotype E is generated by recombination between genotypes B, C and D. Temporal analysis revealed a sequential genotype replacement of C, B, D and E over the study period with genotype D being the dominant genotype since 2007. The novel genotype E was only detected in children younger than three years suffering from lower respiratory tract infections.
  
  
  CONCLUSIONS
  Our results suggest that HCoV-OC43 genotypes are evolving. Such genotype shift may be an adapting mechanism for HCoV-OC43 maintaining its epidemic.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Fondation Mérieux, Lyon, 69002, France.
authors.forename: Gláucia
authors.initials: G
authors.lastname: Paranhos-Baccalà
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China. Electronic address: renliliipb@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing 100730, PR China. Electronic address: wangjw28@163.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018352:Coronavirus Infections / Q000453:epidemiology / Q000821:virology*; D028962:Coronavirus OC43, Human / Q000235:genetics*; D005260:Female; D016679:Genome, Viral / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000235:genetics; D010802:Phylogeny; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D011995:Recombination, Genetic; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000821:virology*; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D019590:Nucleocapsid Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Genotype; Human coronavirus OC43; Molecular epidemiology; Recombination; Respiratory infection