Extreme Genomic CpG Deficiency in SARS-CoV-2 and Evasion of Host Antiviral Defense.
Mol Biol Evol
; 37(9): 2699-2705, 2020 09 01.
Article
in English
| MEDLINE | ID: covidwho-52538
ABSTRACT
Wild mammalian species, including bats, constitute the natural reservoir of betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2). Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence. Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. The author shows that SARS-CoV-2 has the most extreme CpG deficiency in all known betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression. A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (alphacoronavirus) as possessing the most extreme CpG deficiency, comparable with that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Reassortant Viruses
/
Genome, Viral
/
Coronavirus Infections
/
Pandemics
/
Alphacoronavirus
/
Betacoronavirus
Type of study:
Observational study
Language:
English
Journal:
Mol Biol Evol
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
Molbev
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