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

Zhang, Yue; Li, Jianguo; Xiao, Yan; Zhang, Jing; Wang, Ying; Chen, Lan; Paranhos-Baccalà , Gláucia; Ren, Lili; Wang, Jianwei

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.