title: Diversity and Evolutionary Histories of Human Coronaviruses NL63 and 229E Associated with Acute Upper Respiratory Tract Symptoms in Kuala Lumpur, Malaysia.
abstract: The human alphacoronaviruses HCoV-NL63 and HCoV-229E are commonly associated with upper respiratory tract infections (URTI). Information on their molecular epidemiology and evolutionary dynamics in the tropical region of southeast Asia however is limited. Here, we analyzed the phylogenetic, temporal distribution, population history, and clinical manifestations among patients infected with HCoV-NL63 and HCoV-229E. Nasopharyngeal swabs were collected from 2,060 consenting adults presented with acute URTI symptoms in Kuala Lumpur, Malaysia, between 2012 and 2013. The presence of HCoV-NL63 and HCoV-229E was detected using multiplex polymerase chain reaction (PCR). The spike glycoprotein, nucleocapsid, and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. A total of 68/2,060 (3.3%) subjects were positive for human alphacoronavirus; HCoV-NL63 and HCoV-229E were detected in 45 (2.2%) and 23 (1.1%) patients, respectively. A peak in the number of HCoV-NL63 infections was recorded between June and October 2012. Phylogenetic inference revealed that 62.8% of HCoV-NL63 infections belonged to genotype B, 37.2% was genotype C, while all HCoV-229E sequences were clustered within group 4. Molecular dating analysis indicated that the origin of HCoV-NL63 was dated to 1921, before it diverged into genotype A (1975), genotype B (1996), and genotype C (2003). The root of the HCoV-229E tree was dated to 1955, before it diverged into groups 1-4 between the 1970s and 1990s. The study described the seasonality, molecular diversity, and evolutionary dynamics of human alphacoronavirus infections in a tropical region.
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Maryam Nabiel
authors.initials: MN
authors.lastname: Al-Khannaq
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kim Tien
authors.initials: KT
authors.lastname: Ng
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Xiang Yong
authors.initials: XY
authors.lastname: Oong
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yong Kek
authors.initials: YK
authors.lastname: Pang
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takebe
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Jack Bee
authors.initials: JB
authors.lastname: Chook
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nik Sherina
authors.initials: NS
authors.lastname: Hanafi
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Yokohama City University, Kanagawa, Japan; Department of Health Sciences, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia k2tee@um.edu.my.
authors.forename: Kok Keng
authors.initials: KK
authors.lastname: Tee
mesh_terms: D003139:Common Cold / Q000453:epidemiology* / Q000821:virology*; D028941:Coronavirus 229E, Human / Q000235:genetics*; D018352:Coronavirus Infections / Q000453:epidemiology* / Q000821:virology*; D058957:Coronavirus NL63, Human / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D010802:Phylogeny; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014764:Viral Proteins