Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes

Abstract

Human coronavirus OC43 (HCoV-OC43) is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.

Use of whole-genome sequencing in the molecular investigation of care-associated HCoV-OC43 infections in a hematopoietic stem cell transplant unit

“…Phylogenetic trees based on the whole genome and S gene HCoV−OC43 show that genotypes B, G, E and F currently circulate among French patients, in agreement with other report [29]. Even if HCoV−OC43 was previously detected among patients with haematology malignancy, the involvement of HCoV−OC43 genotypes in this type of infection was rarely investigated [38][39][40].…”

“…Strains described here represent probably a part of strains currently circulating among European people. However, our data show that both kinds of HCoV−OC43 strains circulate among patients included in the study: those belonging to the genotype G closely related to Asian strains and other belonging to the genotype F more related to other European strains previously described [25,26,28,29,41]. Amino acid substitution analyses showed that some substitutions especially in the S protein could be specific of strains circulating in European population but the number of strains analyzed here and the number of sequences obtained from European isolates of HCoV−OC43 are too small and further studies will be needed to confirm our data.…”

“…Since S protein sequences of other French HCoV−OC43 isolates have been previously published, phylogenetic analyses show that MDS sequences of the cluster 2013 are clustered to other French sequences on the phylogenetic tree, whereas sequences of the cluster 2014 appear more related to Malaysian, Chinese and American sequences (Fig. 2B) [29]. When signature amino acid substitutions were analyzed, for the genotype B, 3 amino acid substitutions appear on the sequence MDS16: absence of substitution D471 N, substitutions L482 F that is common to other sequences of genotype B, C, F and G and L505S that is also observed on sequences of genotype C. For the genotype E, the amino acid (Fig.…”

Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses

“…Genotype E, identified in 2014, emerged by recombination amongst the genotype B, C, and D viruses with different breakpoints in the genes compared to the generation of genotype D [76] (Figure 4). A study in France, between 2001 and 2013, demonstrated that OC43 strains have more recombination patterns in Lower Normandy, and circulating OC43 viruses have a high genetic diversity [17].…”

“…Currently, six different CoV strains are known to infect humans. These include: HCoV-229E (229E), HCoV-OC43 (OC43), severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-NL63 (NL63), HCoV-HKU1 (HKU1), and Middle East respiratory syndrome coronavirus (MERS-CoV) [17]. 229E and OC43 are the prototype viruses from the two main HCoV lineages (Alpha and Beta, respectively) that cause 15-29% of all common colds, and are the best characterized [18].…”