Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia

Abstract

BackgroundDespite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking.MethodsThe study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference.ResultsA total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed.ConclusionsThe present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.

Evolution and variation of 2019-novel coronavirus

“…HKU1 is related to a variety of children's and adult diseases and distributed globally [16]. In the United States, 0.5% HKU1 positive rate was detected in 15 287 respiratory samples during 2009-2013 [17]; in Kenya, Africa, 2.1% of the 417 respiratory samples collected in [2009][2010][2011][2012] were infected by HKU1 [18]; in Southeast Asia, the positive rate of HKU1 was 1.1% in 2060 adult acute respiratory samples from Malaysia in 2012-2013 [19]. The positive detection rate was 1.9% in Japan and 4342 from 2010 to 2013, and 2.5% in Korea [20,21].…”

Molecular Evolution of Human Coronavirus Genomes

“…As for SARS-CoV and MERS-CoV, molecular dating studies estimated that they diverged from bat CoVs in the last three decades [14,88]. Finally, the MRCA of HCoV-HKU1 extant lineages was estimated to have existed in the 1950s [60]. Clearly, these dates should be regarded as estimates and confidence intervals are often wide.…”

“…Recombination seems to be rampant in HCoV-OC43 viruses and contributed to originate the A to E viral genotypes, as well as viruses that do not belong to these major genotypes [58][59][60]. To our knowledge, no study has analyzed the fitness of recombinant viruses or, more generally, of viruses belonging to distinct genotypes.…”

Intensive care admission for Coronavirus OC43 respiratory tract infections

“…These outbreaks mainly occur when the temperature is low. However, Coronavirus OC43 outbreaks have been reported in tropical climates: Malaysia [7] and Brazil [8] in 2012-2013. The 2016 Southern Hemisphere's winter in Reunion Island was among the coldest of the last decade [9].…”