title: Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination.
abstract: Although human coronavirus OC43-OC43 (HCoV-OC43) is the coronavirus most commonly associated with human infections, little is known about its molecular epidemiology and evolution. We conducted a molecular epidemiology study to investigate different genotypes and potential recombination in HCoV-OC43. Twenty-nine HCoV-OC43 strains from nasopharyngeal aspirates, collected from 2004 to 2011, were subjected to RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid gene analysis. Phylogenetic analysis showed at least three distinct clusters of HCoV-OC43, although 10 unusual strains displayed incongruent phylogenetic positions between RdRp and spike genes. This suggested the presence of four HCoV-OC43 genotypes (A to D), with genotype D most likely arising from recombination. The complete genome sequencing of two genotype C and D strains and bootscan analysis showed recombination events between genotypes B and C in the generation of genotype D. Of the 29 strains, none belonged to the more ancient genotype A, 5 from 2004 belonged to genotype B, 15 from 2004 to 2006 belonged to genotype C, and 1 from 2004 and all 8 from 2008 to 2011 belonged to the recombinant genotype D. Molecular clock analysis using spike and nucleocapsid genes dated the most recent common ancestor of all genotypes to the 1950s, genotype B and C to the 1980s, genotype B to the 1990s, and genotype C to the late 1990s to early 2000s, while the recombinant genotype D strains were detected as early as 2004. This represents the first study to describe natural recombination in HCoV-OC43 and the evolution of different genotypes over time, leading to the emergence of novel genotype D, which is associated with pneumonia in our elderly population.
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong. skplau@hkucc.hku.hk
authors.forename: Susanna K P
authors.initials: SK
authors.lastname: Lau
authors.forename: Paul
authors.initials: P
authors.lastname: Lee
authors.forename: Alan K L
authors.initials: AK
authors.lastname: Tsang
authors.forename: Cyril C Y
authors.initials: CC
authors.lastname: Yip
authors.forename: Herman
authors.initials: H
authors.lastname: Tse
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Lee
authors.forename: Lok-Yee
authors.initials: LY
authors.lastname: So
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Chan
authors.forename: Patrick C Y
authors.initials: PC
authors.lastname: Woo
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D016000:Cluster Analysis; D003139:Common Cold / Q000821:virology*; D018352:Coronavirus Infections / Q000821:virology*; D028962:Coronavirus OC43, Human / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000821:virology; D019590:Nucleocapsid Proteins / Q000235:genetics; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D012321:DNA-Directed RNA Polymerases