Abstract

This paper reports on an investigation of the role of codon usage evolution on the suggested bovine-to-human spillover of Bovine coronavirus (BCoV), an enteric/respiratory virus of cattle, resulting in the emergence of the exclusively respiratory Human coronavirus OC43 (HCoV-OC43). Analyses based on full genomes of BCoV and HCoV-OC43 and on both human and bovine mRNAs sequences of cholecystokinin (CCK) and surfactant protein 1 A (SFTP1-A), representing the enteric and respiratory tract codon usage, respectively, have shown natural selection leading to optimization or deoptimization of viral codon usage to the human enteric and respiratory tracts depending on the virus genes under consideration. A higher correlation was found for the nucleotide distance at the 3rd nucleotide position of codons and codon usage optimization to the human respiratory tract when BCoV and HCoV-OC43 were compared. An MCC tree based on relative synonymous codon usage (RSCU) data integrating data from both viruses and hosts into a same analysis indicated three putative host/virus contact dates ranging from 1.54E8 to 2.44E5 years ago, suggesting that an ancestor coronavirus might have followed human evolution.

Highlights

  • Human coronavirus OC43 (Nidovirales: Coronaviridae: Coronavirinae: Betacoronavirus: Betacoronavirus 1, HCoV-OC43) is an epitheliotropic respiratory virus widespread in human populations and involved in common cold (Mäkelä et al, 1998), while Bovine coronavirus (BCoV), another host-type of Betacoronavirus 1, is commonly found infecting both the respiratory and enteric tracts of cattle and might lead to respiratory disease and diarrhea/dysentery (Dea et al, 1995; Saif, 2010)

  • This paper reports on an investigation of the role of codon usage evolution on the suggested bovine-to-human spillover of Bovine coronavirus (BCoV), an enteric/respiratory virus of cattle, resulting in the emergence of the exclusively respiratory Human coronavirus OC43 (HCoV-OC43)

  • For both BCoV and HCoV-OC43 nsp7, the lowest Codon adaptation index (CAI) distance (-0.039) was found for both the human and respiratory and enteric tracts regarding the lower CAI limit calculated for all seven human coronaviruses, while the highest CAI distances for the lower human coronaviruses CAI was found for BCoV and HCoV-OC43 N for both the human and respiratory and enteric tracts (-0.282 and -0.302, respectively) and BCoV nsp15 (-0,282) for the human respiratory tract

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Summary

Introduction

Human coronavirus OC43 (Nidovirales: Coronaviridae: Coronavirinae: Betacoronavirus: Betacoronavirus 1, HCoV-OC43) is an epitheliotropic respiratory virus widespread in human populations and involved in common cold (Mäkelä et al, 1998), while Bovine coronavirus (BCoV), another host-type of Betacoronavirus 1, is commonly found infecting both the respiratory and enteric tracts of cattle and might lead to respiratory disease and diarrhea/dysentery (Dea et al, 1995; Saif, 2010). Betacoronaviruses have a history of spillover to humans leading to the emergence of pathogens, such as the Middle East Respiratory Syndrome Human Coronavirus (MERS-CoV) and the Severe Acute Respiratory Syndrome Human Coronavirus (HCoV-SARS) (Li et al, 2005; Gossner et al, 2016). Such a pathogen emergence is limited by ecological and genetic factors (Gandon et al, 2013), and codon usage, i.e., the deviation from the random use of different codons for the 2 to 6-fold degenerate codons (Hershberg and Petrov, 2009; Roth et al, 2012), is one genetic factor that might help to explain this process

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