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. 2015 Jun;70(6):641-50.
doi: 10.1016/j.jinf.2014.12.005. Epub 2014 Dec 18.

Genotype shift in human coronavirus OC43 and emergence of a novel genotype by natural recombination

Affiliations

Genotype shift in human coronavirus OC43 and emergence of a novel genotype by natural recombination

Yue Zhang et al. J Infect. 2015 Jun.

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.

Keywords: Genotype; Human coronavirus OC43; Molecular epidemiology; Recombination; Respiratory infection.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Phylogenetic analysis of different HCoV-OC43 strains based on full-length S, RdRp and N genes. Trees were constructed using the maximum-likelihood method. Strains identified in this study are presented in bold. A, B, C, D and E represent genotypes.
Figure 2
Figure 2
Phylogenetic analysis of multiple gene regions of HCov-OC43 strains. A total of 23 gene regions are analyzed, including nsp1 to nsp16, ns2α, HE, S, NS5α, E, M and N of ten genomes of HCoV-OC43. The neighbor-joining method (Kimura's two-parameter) was used to construct the trees with 1000 bootstrap values.
Figure 3
Figure 3
Recombination analyses of HCoV-OC43 genomes. Bootscan plot analysis of the whole genome sequences identified in this study in comparison to reference strains in genotypes B, C and D. Graphs were generated using 1783A/10, 2058A/10, 3074A/12 and 3194A/12 as query sequences. The bootstrap value is 1000 for a window of 200 bp.
Figure 4
Figure 4
Yearly distribution of HCoV-OC43 genotypes during 2005–2012. The left and right vertical axis show the number of HCoV-OC43 cases and the detection rate among the recruited cases.

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