32nd International Dynamics & Evolution of Human Viruses

UNVEILING NOVEL HCOV-OC43 GENOTYPES: THE HIDDEN WORLD OF INTRA-HOST EVOLUTION

Not scheduled

20m

Abbaye de Royaumont, Asnières-sur-Oise, France

Oral Phylodynamics & phylogeography

Speaker

Dr Frida Belinky (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

Description

HCoV-OC43 is a common cold coronavirus that has persisted in the human population for decades. This study investigates HCoV-OC43's genomic diversity and recombination patterns to elucidate the emergence of new genotypes and shed light on intra-host diversification, which underpins the ongoing evolution of HCoV-OC43. Employing consensus sequencing and high-throughput single genome sequencing (HT-SGS) on samples from the Michigan Household Influenza Vaccine Evaluation (HIVE) cohort, this study characterizes 84 whole genome consensus sequences and 202 intra-host haplotypes. Analyses of publicly available and consensus whole-genome sequences revealed nine novel genotypes characterized by distinct recombination patterns. All novel genotypes included a common breakpoint within the HE gene, while three displayed another common breakpoint in the S gene. Additionally, HT-SGS targeting a genomic region spanning the HE and S genes revealed four instances of dual infection, where two distinct genotypes were identified within a single individual. Notably, in one dual infection case, HT-SGS demonstrated 16 recombinant haplotypes, with 9 distinct breakpoints in S and 6 in HE. This is the first reported instance of intra-host recombination of HCoV-OC43, exemplifying the prevalence of recombination within a single host. Furthermore, several individuals exhibited higher rates of nonsynonymous to synonymous mutations, suggesting intra-host positive selection, including several putative immune escape cases where mutations altering the epitope or glycosylation sites were identified. Interestingly, positive selection was more predominant in young individuals, suggesting that exposure histories or immune system development influence the antigenic escape landscape of HCoV-OC43. Taken together, these findings highlight how both positive selection and recombination occur intra-host in HCoV-OC43 infection, leading to the novel genotypes identified in the human population.