The low abundance of CpG in the SARS-CoV-2 genome is not an evolutionarily signature of ZAP

Sci Rep. 2022 Feb 14;12(1):2420. doi: 10.1038/s41598-022-06046-5.

Abstract

The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG dinucleotides, nor a link between the activity of ZAP and the low CpG abundance of the SARS-CoV-2 genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • COVID-19 / genetics*
  • COVID-19 / virology
  • Dinucleoside Phosphates / genetics*
  • Dinucleoside Phosphates / metabolism
  • Evolution, Molecular
  • Genome, Viral / genetics*
  • Host-Pathogen Interactions / genetics
  • Humans
  • Nucleotide Motifs / genetics
  • Protein Binding
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / physiology
  • Virus Replication / genetics

Substances

  • Dinucleoside Phosphates
  • RNA, Viral
  • RNA-Binding Proteins
  • ZC3HAV1 protein, human
  • cytidylyl-3'-5'-guanosine