The DOI matches its Crossref record; 52 of the 55 references it cites were found in a registry or an index, and 2 are not checked yet.
Evasion of Type I Interferon by SARS-CoV-2
Open accessAbstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and host immune response determine coronavirus disease 2019 (COVID-19), but studies evaluating viral evasion of immune response are lacking. Here, we use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. We identify two sets of viral proteins that antagonize IFN-I signaling through blocking signal transducer and activator of transcription 1 (STAT1)/STAT2 phosphorylation or nuclear translocation. Remarkably, SARS-CoV-2 nsp1 and nsp6 suppress IFN-I signaling more efficiently than SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Thus, when treated with IFN-I, a SARS-CoV-2 replicon replicates to a higher level than chimeric replicons containing nsp1 or nsp6 from SARS-CoV or MERS-CoV. Altogether, the study provides insights on SARS-CoV-2 evasion of IFN-I response and its potential impact on viral transmission and pathogenesis.
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“Functional testing further supported the counteracting activity of ORF3b, ORF6, NSP1, or NSP13 on type I IFN activation, of which particularly ORF6 suppressed STAT1 and STAT2 phosphorylation and STAT1 nuclear translocation, (Konno et al., 2020; Lei et al., 2020; Xia et al., 2020).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Xia et al., 2020
Experimental — accuracy not yet measuredIn the citing paper
“Interaction mapping further suggested that NSP13 interacts with TBK1, NSP15 with NRDP1 (an E3 ubiquitin ligase controlling the balance between JAK2-associated cytokine receptor degradation and ectodomain shedding), ORF9b with TOMM70 (an important receptor of the outer mitochondrial membrane), and ORF6 with either KPNA2 or the IFN-induced NUP98-RAE1 nuclear export complex, which are both involved”
From COVID-19 and the human innate immune system (2021) · cites this paper as Xia et al., 2020
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Cites
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IKKε and TBK1 are essential components of the IRF3 signaling pathway
Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M., & Maniatis, T. (2003) · Nature Immunology · doi:10.1038/ni921 · Cited by 2,680
Research works printed but not linked: 1
- Lokugamage, 2020, SARS-CoV-2 is sensitive to type I interferon pretreatment, bioRxiv
Cited by
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Mechanisms of SARS-CoV-2 Transmission and Pathogenesis
Harrison, A. G., Lin, T., & Wang, P. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.10.004 · Cited by 1,261
The biological and clinical significance of emerging SARS-CoV-2 variants
Tao, K., Tzou, P. L., Nouhin, J., Gupta, R. K., de Oliveira, T., Kosakovsky Pond, S. L., Fera, D., & Shafer, R. W. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00408-x · Cited by 1,009
COVID-19 and the human innate immune system
Schultze, J. L., & Aschenbrenner, A. C. (2021) · Cell · doi:10.1016/j.cell.2021.02.029 · Cited by 714
“Interaction mapping further suggested that NSP13 interacts with TBK1, NSP15 with NRDP1 (an E3 ubiquitin ligase controlling the balance between JAK2-associated cytokine receptor degradation and ectodomain shedding), ORF9b with TOMM70 (an important receptor of the outer mitochondrial membrane), and ORF6 with either KPNA…”
BackgroundInnate immunity: the first line of defense against SARS-CoV-2
Diamond, M., & Kanneganti, T. (2022) · Nature Immunology · doi:10.1038/s41590-021-01091-0 · Cited by 639
Immunological mechanisms of vaccine-induced protection against COVID-19 in humans
Sadarangani, M., Marchant, A., & Kollmann, T. R. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00578-z · Cited by 560
Metadata
- Authors
- Xia, H., Cao, Z., Xie, X., Zhang, X., Chen, J. Y.-C., Wang, H., Menachery, V. D., Rajsbaum, R., & Shi, P.-Y.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Jilin University (CN)
- Corresponding author
- Xia, Hongjie
- Shi, Pei-Yong
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 33
- Issue
- 1
- Pages
- 108234
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7501843
- OpenAlex
- W3087744389
- Cited by
- 957
- References
- 55
- Citations by year
- 2026: 36 · 2025: 79 · 2024: 116 · 2023: 167 · 2022: 253 · 2021: 266 · 2020: 40
- FWCI
- 63.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AI142759, AI134907, AI145617, UL1TR001439)
- Summerfield G. Roberts Foundation (R01AI134907, R21AI126012-01A1, R21AI132479-01, R00AG049092, U19AI100625, R24AI120942)
- Sealy and Smith Foundation
- John S. Dunn Foundation
- Gillson Longenbaugh Foundation
- Amon G. Carter Foundation
- University of Texas System
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, interferon signaling, NSP6, nsp13, ORF6, TBK1, IRF3 phosphorylation, KPNA2, Nsp1, viral immune evasion, COVID-19 pandemic, SARS-CoV, MERS-CoV, viral replication
- MeSH terms
- A549 Cells, Betacoronavirus, COVID-19, SARS-CoV-2, Coronavirus Nucleocapsid Proteins, Animals, Cricetulus, Cricetinae, Humans, Interferon Type I, Methyltransferases, Pneumonia, Viral, Protein Binding, Viral Proteins, Protein Serine-Threonine Kinases, Viral Nonstructural Proteins, Coronavirus Infections, RNA Helicases, alpha Karyopherins, Capsid Proteins, STAT Transcription Factors, Interferon Regulatory Factor-3, Immune Evasion, HEK293 Cells, Pandemics
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