SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant.
Adult
Amino Acid Sequence
/ genetics
Animals
Betacoronavirus
/ genetics
COVID-19
Chiroptera
/ virology
Codon, Nonsense
/ genetics
Coronavirus Infections
/ pathology
Eutheria
/ virology
Humans
Interferon Type I
/ antagonists & inhibitors
Male
Pandemics
Pneumonia, Viral
/ virology
SARS-CoV-2
Viral Regulatory and Accessory Proteins
/ genetics
COVID-19
ORF3b
SARS-CoV-2
evolution
type I interferon
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
22 09 2020
22 09 2020
Historique:
received:
18
05
2020
revised:
22
07
2020
accepted:
01
09
2020
pubmed:
18
9
2020
medline:
7
10
2020
entrez:
17
9
2020
Statut:
ppublish
Résumé
One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays reveal that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of approximately 17,000 SARS-CoV-2 sequences identify a natural variant in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis.
Identifiants
pubmed: 32941788
pii: S2211-1247(20)31174-8
doi: 10.1016/j.celrep.2020.108185
pmc: PMC7473339
pii:
doi:
Substances chimiques
Codon, Nonsense
0
Interferon Type I
0
Viral Regulatory and Accessory Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108185Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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