All hands on deck: SARS-CoV-2 proteins that block early anti-viral interferon responses.
Curr Res Virol Sci
; 2: 100015, 2021.
Article
in English
| MEDLINE | ID: covidwho-1597926
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is responsible for the current pandemic coronavirus disease of 2019 (COVID-19). Like other pathogens, SARS-CoV-2 infection can elicit production of the type I and III interferon (IFN) cytokines by the innate immune response. A rapid and robust type I and III IFN response can curb viral replication and improve clinical outcomes of SARS-CoV-2 infection. To effectively replicate in the host, SARS-CoV-2 has evolved mechanisms for evasion of this innate immune response, which could also modulate COVID-19 pathogenesis. In this review, we discuss studies that have reported the identification and characterization of SARS-CoV-2 proteins that inhibit type I IFNs. We focus especially on the mechanisms of nsp1 and ORF6, which are the two most potent and best studied SARS-CoV-2 type I IFN inhibitors. We also discuss naturally occurring mutations in these SARS-CoV-2 IFN antagonists and the impact of these mutations in vitro and on clinical presentation. As SARS-CoV-2 continues to spread and evolve, researchers will have the opportunity to study natural mutations in IFN antagonists and assess their role in disease. Additional studies that look more closely at previously identified antagonists and newly arising mutants may inform future therapeutic interventions for COVID-19.
3CLpro, 3-chymotrypsin like protease; COVID-19, coronavirus disease of 2019; IFN, interferon; IFNAR, interferon alpha/beta receptor; IFNLR, interferon lambda receptor; IRF, interferon response factor; ISRE, interferon stimulated response element; Immune evasion; MAVS, mitochondrial antiviral-signaling protein; MDA-5, melanoma differentiation-associated protein 5; ORF, open reading frame; ORF6; PLpro, papain-like protease; RIG-I, retinoic acid-inducible gene I; SARS-CoV-2; SARS-CoV-2, SARS coronavirus 2; SRP, signal recognition particle; STAT, signal transducer and regulator of transcription; SeV, Sendai virus; TAB1, TGF-beta activated kinase 1 binding protein 1; TAK1, TGF-beta activated kinase 1; TBK1, TANK-binding kinase 1; TLR, toll-like receptor; TRIF, TIR domain-containing adapter-inducing interferon beta; Type I interferon; UTR, untranslated region; eIF, eukaryotic initiation factor; nsp, non-structural protein; nsp1
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
Language:
English
Journal:
Curr Res Virol Sci
Year:
2021
Document Type:
Article
Affiliation country:
J.crviro.2021.100015
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