Journal
VIRUSES-BASEL
Volume 13, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/v13091847
Keywords
bats; coronaviruses; codon usage; CpG dinucleotide; evolution; SARS-CoV-2
Categories
Funding
- Indian Council of Agricultural Research (ICAR)-National Institute of High Security Animal Diseases
- ICAR-National Agricultural Science Fund [NASF/ABA-8028/2020-21]
- Japan Society for the Promotion of Science (JSPS) KAKENHI grant [18H02395]
- UK Research and Innovation-Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BBS/E/I/00007038, BBS/E/I/00007039]
- BBSRC [BBS/E/I/00007038, BBS/E/I/00007039] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [18H02395] Funding Source: KAKEN
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This study investigates the codon usage trends in bat-hosted coronaviruses, revealing the potential ancestors of SARS-CoV-2 and uncovering specific characteristics of the virus. Furthermore, it dissects the evolution and specificity of various CoVs in hosts, shedding light on the latent diversity of coronaviruses in mammals that has yet to be fully explored.
Many viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes. Our study is aimed at deciphering some of these signatures. Using a variety of genetic methods we demonstrated that trends in codon usage across chiroptera-hosted CoVs are collaboratively driven by geographically different host-species and temporal-spatial distribution. We not only found that chiroptera-hosted CoVs are the ancestors of SARS-CoV-2, but we also revealed that SARS-CoV-2 has the codon usage characteristics similar to those seen in CoVs infecting the Rhinolophus sp. Surprisingly, the envelope gene of beta-CoVs infecting Rhinolophus sp., including SARS-CoV-2, had extremely high CpG levels, which appears to be an evolutionarily conserved trait. The dissection of the furin cleavage site of various CoVs infecting hosts revealed host-specific preferences for arginine codons; however, arginine is encoded by a wider variety of synonymous codons in the murine CoV (MHV-A59) furin cleavage site. Our findings also highlight the latent diversity of CoVs in mammals that has yet to be fully explored.
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