Coronavirus genomes carry the signatures of their habitats

• Published in: PloS one Vol. 15; no. 12; p. e0244025
• Main Authors: Wei, Yulong, Silke, Jordan R, Aris, Parisa, Xia, Xuhua
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.12.2020; Public Library of Science (PLoS)
• Subjects: Animals; APOBEC Deaminases; Apolipoprotein B; Biology; Biology and life sciences; Cattle; Coronaviridae; Coronavirus - classification; Coronavirus - genetics; Coronavirus - pathogenicity; Coronaviruses; COVID-19; COVID-19 - genetics; COVID-19 - pathology; COVID-19 - virology; CpG islands; Cytidine Deaminase - genetics; Disease control; Dogs; Editing; Environmental aspects; Enzymes; Evolution, Molecular; Genetic aspects; Genome, Viral - genetics; Genomes; HIV; Human immunodeficiency virus; Humans; Hypoxia; Immune response; Immune system; Infections; Mammals; Medicine and health sciences; Mice; Microbiological research; Middle East Respiratory Syndrome Coronavirus - genetics; Middle East Respiratory Syndrome Coronavirus - pathogenicity; Mutation; Polypeptides; Proteins; Repressor Proteins - genetics; Research and Analysis Methods; RNA editing; RNA-Binding Proteins - genetics; SARS-CoV-2 - genetics; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome-related coronavirus - genetics; Severe acute respiratory syndrome-related coronavirus - pathogenicity; Swine - virology; Tissues; Vaccine development; Vaccines; Viral diseases; Viral infections; Viruses; Zinc finger proteins; Canada; Ottawa Ontario Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0244025

Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of infection. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA editing enzyme-catalytic polypeptide-like 3 (APOBEC3). The former binds to CpG dinucleotides to facilitate the degradation of viral transcripts while the latter frequently deaminates C into U residues which could generate notable viral sequence variations. We tested the hypothesis that both APOBEC3 and ZAP impose selective pressures that shape the genome of an infecting coronavirus. Our investigation considered a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, and MERS infecting Homo sapiens, Bovine CoV infecting Bos taurus, MHV infecting Mus musculus, HEV infecting Sus scrofa, and CRCoV infecting Canis lupus familiaris). We show that coronaviruses that regularly infect tissues with abundant AVPs have CpG-deficient and U-rich genomes; whereas those that do not infect tissues with abundant AVPs do not share these sequence hallmarks. Among the coronaviruses surveyed herein, CpG is most deficient in SARS-CoV-2 and a temporal analysis showed a marked increase in C to U mutations over four months of SARS-CoV-2 genome evolution. Furthermore, the preferred motifs in which these C to U mutations occur are the same as those subjected to APOBEC3 editing in HIV-1. These results suggest that both ZAP and APOBEC3 shape the SARS-CoV-2 genome: ZAP imposes a strong CpG avoidance, and APOBEC3 constantly edits C to U. Evolutionary pressures exerted by host immune systems onto viral genomes may motivate novel strategies for SARS-CoV-2 vaccine development.