Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: phylogenetic, spatiotemporal and transmission network analyses

Abstract

Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.

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

“…The divergence time of sequences included in the phylogenetic analyses was calculated to accumulate to collect additional information showing the common origin of clinical isolates. Our results are similar to those previously described, validating the tMRCA method used [25,28]. Indeed, our results show that each cluster of sequences has diverged from a distinct ancestor in 2010.9 for the cluster 2013 and in 2011.5 for the cluster 2014.…”

“…3A). Likewise, sequences of the cluster 2013 show the specific substitution of the genotype F (Y177 H) and 9 additional amino acids substitutions relative to the others of the genotype F [25]. Notably, MDS6, MDS12 and MDS14 sequences show 12 additional substitutions relative to the genotype F, which are absent on the MDS4 sequence.…”

“…We followed the methodology used in [25]. Notably, we added Asiatic sequences that were also used in [25] and [26].…”

“…We followed the methodology used in [25]. Notably, we added Asiatic sequences that were also used in [25] and [26]. We estimated divergence times using BEAST 1.8.4 [12] on both whole genome and S gene [27].…”

“…The tree obtained from full-length genomes showed that MDS sequences are divided into 4 known genotypes B, F and G ( Fig. 2A) [25,26,28]. MDS4, MDS6, MDS14 and MDS12 sequences, belonging to the genotype F, are grouped into the same cluster separated from other sequences of genotype F with high bootstrap value (79.6 %).…”