SARS-CoV-2 Is Restricted by Zinc Finger Antiviral Protein despite Preadaptation to the Low-CpG Environment in Humans.
Animals
Betacoronavirus
/ classification
COVID-19
Cell Line
Coronavirus
/ classification
Coronavirus Infections
/ virology
CpG Islands
Gene Expression
/ drug effects
Genome, Viral
Humans
Interferons
/ pharmacology
Pandemics
Phylogeny
Pneumonia, Viral
/ virology
Protein Isoforms
RNA, Viral
/ genetics
RNA-Binding Proteins
/ chemistry
SARS-CoV-2
Virus Replication
/ drug effects
COVID-19
CpG suppression
SARS-CoV-2
ZAP
evolution
interferon
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
16 10 2020
16 10 2020
Historique:
entrez:
17
10
2020
pubmed:
18
10
2020
medline:
5
11
2020
Statut:
epublish
Résumé
Recent evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sensitive to interferons (IFNs). However, the most effective types of IFNs and the underlying antiviral effectors remain to be defined. Here, we show that zinc finger antiviral protein (ZAP), which preferentially targets CpG dinucleotides in viral RNA sequences, restricts SARS-CoV-2. We further demonstrate that ZAP and its cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II, and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP expression. Comprehensive sequence analyses revealed that SARS-CoV-2 and its closest relatives from horseshoe bats showed the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, endogenous ZAP expression restricted SARS-CoV-2 replication in human lung cells, particularly upon treatment with IFN-α or IFN-γ. Both the long and the short isoforms of human ZAP reduced SARS-CoV-2 RNA expression levels, but the former did so with greater efficiency. Finally, we show that the ability to restrict SARS-CoV-2 is conserved in ZAP orthologues of the reservoir bat and potential intermediate pangolin hosts of human coronaviruses. Altogether, our results show that ZAP is an important effector of the innate response against SARS-CoV-2, although this pandemic pathogen emerged from zoonosis of a coronavirus that was preadapted to the low-CpG environment in humans.
Identifiants
pubmed: 33067384
pii: mBio.01930-20
doi: 10.1128/mBio.01930-20
pmc: PMC7569149
pii:
doi:
Substances chimiques
Protein Isoforms
0
RNA, Viral
0
RNA-Binding Proteins
0
ZC3HAV1 protein, human
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_PC_14105
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15068
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S000844/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Nchioua et al.
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