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Five-year (2017-2022) evolutionary dynamics of human coronavirus HKU1 in southern France with emergence of viruses harboring spike H512R substitution
  • +7
  • Houmadi Hikmat,
  • Lorlane Le Targa,
  • Céline BOSCHI,
  • Justine PY,
  • Aurélie Morand,
  • Jean-Christophe LAGIER,
  • Sarah Aherfi,
  • Jacques Fantini,
  • Bernard La Scola,
  • Philippe Colson
Houmadi Hikmat
Aix-Marseille Universite Fondation
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Lorlane Le Targa
Aix-Marseille Universite Fondation
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Céline BOSCHI
Aix-Marseille Universite Fondation
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Justine PY
Aix-Marseille Universite Fondation
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Aurélie Morand
Assistance Publique Hopitaux de Marseille
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Jean-Christophe LAGIER
Aix-Marseille Universite Fondation
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Sarah Aherfi
Aix-Marseille Universite Fondation
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Jacques Fantini
Aix-Marseille Universite Fondation
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Bernard La Scola
Aix-Marseille Universite Fondation
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Philippe Colson
Aix-Marseille Universite Fondation

Corresponding Author:[email protected]

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Abstract

Objectives HCoV-HKU1 diversity and evolution was scarcely studied. We performed next-generation sequencing (NGS) and analysis of HCoV-HKU1 genomes over five years. Methods NGS used Illumina technology on NovaSeq 6000 following whole genome PCR amplification by a in-house set of primers designed using Gemi and PrimalScheme. Genome assembly and analyses used CLC Genomics, Mafft, BioEdit, Nextstrain, Nextclade, MEGA and iTol bioinformatic tools. Spike molecular modelling and dynamics simulations used Molegro Molecular Viewer/Hyperchem. Results Twenty-eight PCR systems allowed obtaining 158 HCoV-HKU1 genomes including 69 and 89 of genotype A and B, respectively. Both genotypes co-circulated during the study period but one predominated each year. 1,683 amino acid substitutions including 80 in ≥10 genomes were detected in genotype A relatively to a 2004 reference. H512R in spike, first detected in 2009 and reported as involved in antibody neutralization, was found in all genotype A, almost always with V387I and K478N, and was predicted here to significantly improve cellular TMPRSS2 protein binding. 1,802 amino acid substitutions including 64 in ≥10 genomes were detected in genotype B relatively to a 2005 reference. Conclusion This study substantially expands the global set of HCoV-HKU1 genomes. Genomics with protein structural analyses contributed to our understanding of HCoV-HKU1 evolution.
19 Jul 2024Submitted to Journal of Medical Virology
27 Jul 2024Submission Checks Completed
27 Jul 2024Assigned to Editor
27 Jul 2024Review(s) Completed, Editorial Evaluation Pending
29 Jul 2024Reviewer(s) Assigned
31 Aug 2024Editorial Decision: Revise Major