Abstract

The recent discovery of novel alphacoronaviruses (alpha-CoVs) in European and Asian rodents revealed that rodent coronaviruses (CoVs) sampled worldwide formed a discrete phylogenetic group within this genus. To determine the evolutionary history of rodent CoVs in more detail, particularly the relative frequencies of virus-host co-divergence and cross-species transmission, we recovered longer fragments of CoV genomes from previously discovered European rodent alpha-CoVs using a combination of PCR and high-throughput sequencing. Accordingly, the full genome sequence was retrieved from the UK rat coronavirus, along with partial genome sequences from the UK field vole and Poland-resident bank vole CoVs, and a short conserved ORF1b fragment from the French rabbit CoV. Genome and phylogenetic analysis showed that despite their diverse geographic origins, all rodent alpha-CoVs formed a single monophyletic group and shared similar features, such as the same gene constellations, a recombinant beta-CoV spike gene, and similar core transcriptional regulatory sequences (TRS). These data suggest that all rodent alpha CoVs sampled so far originate from a single common ancestor, and that there has likely been a long-term association between alpha CoVs and rodents. Despite this likely antiquity, the phylogenetic pattern of the alpha-CoVs was also suggestive of relatively frequent host-jumping among the different rodent species.

Highlights

  • Among the viruses that infect both humans and animals, coronaviruses are common and important pathogens

  • The 50 and 30 ends corresponded to the rat Lucheng CoV (KF294380)-derived primer sequences used for amplification of the genome termini and were not confirmed by the rapid amplification of cDNA ends (RACE) method

  • To determine the extent to which the rodent CoVs may have co-diverged with their rodent hosts, indicative of a very long-term virus-host association, we examined the extent of congruence between the virus ORF1b and host mitochondrial cytochrome b phylogenies by inferring tanglegrams (Figure 5A)

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Summary

Introduction

Among the viruses that infect both humans and animals, coronaviruses are common and important pathogens. The first coronavirus (CoV) was discovered during the 1930s [1], and the first human coronavirus was characterized in the 1960s [2]. Five novel human coronaviruses have been discovered. The coronavirus family gained particular notoriety with the emergence of the severe acute respiratory syndrome (SARS) in 2002/2003 and the Middle East respiratory syndrome (MERS) in 2013. Coronaviruses are associated with respiratory disease, causing a range of symptoms from mild common colds to more severe lower respiratory tract infections that can be lethal. CoV infection in a range of non-human mammals and birds is associated with enteric and respiratory diseases as well as hepatitis and neurological disorders [3]

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