title: Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: phylogenetic, spatiotemporal and transmission network analyses.
abstract: Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Xiang Yong
authors.initials: XY
authors.lastname: Oong
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kim Tien
authors.initials: KT
authors.lastname: Ng
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.|AIDS Research Center, National Institute of Infectious Diseases, 162-8640 Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takebe
authors.affiliation: Faculty of Information Science & Technology, Multimedia University, 75450 Melaka, Malaysia.
authors.forename: Liang Jie
authors.initials: LJ
authors.lastname: Ng
authors.affiliation: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kok Gan
authors.initials: KG
authors.lastname: Chan
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Jack Bee
authors.initials: JB
authors.lastname: Chook
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kok Keng
authors.initials: KK
authors.lastname: Tee
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D016000:Cluster Analysis; D018352:Coronavirus Infections / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D028962:Coronavirus OC43, Human / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D003430:Cross-Sectional Studies; D018562:Disease Transmission, Infectious; D019143:Evolution, Molecular; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D058974:Phylogeography; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D062211:Spatio-Temporal Analysis; D009626:Terminology as Topic; D055815:Young Adult
chemical_list: D012367:RNA, Viral