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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
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“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
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30183-5 · Cited by 48,884
Self-citationA novel coronavirus from patients with pneumonia in China, 2019
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001017 · Cited by 28,244
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969
Self-citationWu, Z., & McGoogan, J. M. (2020) · JAMA · doi:10.1001/jama.2020.2648 · Cited by 17,016
Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., Shi, Z., Hú, Z., Zhong, W., & Xiao, G. (2020) · Cell Research · doi:10.1038/s41422-020-0282-0 · Cited by 6,994
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888
STATs: transcriptional control and biological impact
Levy, D. E., & Darnell, J. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm909 · Cited by 3,201
Interferon-stimulated genes: A complex web of host defenses
Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120231 · Cited by 3,067
Antiviral Actions of Interferons
Samuel, C. E. (2001) · Clinical Microbiology Reviews · doi:10.1128/cmr.14.4.778-809.2001 · Cited by 2,743
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
Channappanavar, R., & Perlman, S. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0629-x · Cited by 2,524
Coronavirus infections and immune responses
Li, G., Fan, Y., Lai, Y., Han, T., Li, Z., Zhou, P., Pan, P., Wang, W., Hu, D., Liu, X., et al. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25685 · Cited by 1,963
Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation
Liu, S., Cai, X., Wu, J., Cong, Q., Chen, X., Li, T., Du, F., Ren, J., Wu, Y.-T., Grishin, N. V., et al. (2015) · Science · doi:10.1126/science.aaa2630 · Cited by 1,927
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
Le Bert, N., Tan, A. T., Kunasegaran, K., Tham, C. Y. L., Hafezi, M., Chia, A., Chng, M. H. Y., Lin, M., Tan, N., Linster, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2550-z · Cited by 1,887
Chloroquine is a potent inhibitor of SARS coronavirus infection and spread
Vincent, M. J., Bergeron, É., Benjannet, S., Erickson, B. R., Rollin, P. E., Ksiazek, T. G., Seidah, N. G., & Nichol, S. T. (2005) · Virology Journal · doi:10.1186/1743-422x-2-69 · Cited by 1,831
Assiri, A., Al-Tawfiq, J. A., Al-Rabeeah, A. A., Al-Rabiah, F. A., Al-Hajjar, S., Al-Barrak, A., Flemban, H., Al-Nassir, W. N., Balkhy, H. H., Al-Hakeem, R. F., et al. (2013) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(13)70204-4 · Cited by 1,435
Intracellular pattern recognition receptors in the host response
Meylan, E., Tschopp, J., & Karin, M. (2006) · Nature · doi:10.1038/nature04946 · Cited by 1,196
Activation and evasion of type I interferon responses by SARS-CoV-2
Lei, X., Dong, X., Ma, R., Wang, W., Xiao, X., Tian, Z., Wang, C., Wang, Y., Li, L., Ren, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17665-9 · Cited by 980
Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19
Park, A., & Iwasaki, A. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.05.008 · Cited by 909
Small self-RNA generated by RNase L amplifies antiviral innate immunity
Malathi, K., Dong, B., Gale, M., & Silverman, R. H. (2007) · Nature · doi:10.1038/nature06042 · Cited by 663
Kopecky-Bromberg, S. A., Martínez‐Sobrido, L., Frieman, M. B., Baric, R. S., & Palese, P. (2006) · Journal of Virology · doi:10.1128/jvi.01782-06 · Cited by 662
Chu, H., Chan, J. F., Wang, Y., Yuen, T. T., Chai, Y., Hou, Y., Shuai, H., Yang, D., Hu, B., Huang, X., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa410 · Cited by 659
Self-citationAn Infectious cDNA Clone of SARS-CoV-2
Xie, X., Muruato, A., Lokugamage, K. G., Narayanan, K., Zhang, X., Zou, J., Liu, J., Schindewolf, C., Bopp, N. E., Aguilar, P. V., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.04.004 · Cited by 647
Self-citationAngelini, M. M., Akhlaghpour, M., Neuman, B. W., & Buchmeier, M. J. (2013) · mBio · doi:10.1128/mbio.00524-13 · Cited by 539
Essential Role for the dsRNA-Dependent Protein Kinase PKR in Innate Immunity to Viral Infection
Balachandran, S., Roberts, P. C., Brown, L. E., Truong, H., Pattnaik, A. K., Archer, D. R., & Barber, G. N. (2000) · Immunity · doi:10.1016/s1074-7613(00)00014-5 · Cited by 527
SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
Yuen, C., Lam, J.-Y., Wong, W., Mak, L., Wang, X., Chu, H., Cai, J., Jin, D., To, K. K., Chan, J. F., et al. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1780953 · Cited by 525
Karyopherins and nuclear import
Chook, Y. M. (2001) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(01)00264-0 · Cited by 525
Type 1 interferons as a potential treatment against COVID-19
Sallard, E., Lescure, F.-X., Yazdanpanah, Y., Mentré, F., & Peiffer‐Smadja, N. (2020) · Antiviral Research · doi:10.1016/j.antiviral.2020.104791 · Cited by 510
Frieman, M. B., Yount, B. L., Heise, M. T., Kopecky-Bromberg, S. A., Palese, P., & Baric, R. S. (2007) · Journal of Virology · doi:10.1128/jvi.01012-07 · Cited by 509
Pruijssers, A. J. P., George, A. S., Schäfer, A., Leist, S. R., Gralinski, L. E., Dinnon, K. H., Yount, B. L., Agostini, M. L., Stevens, L. J., Chappell, J. D., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107940 · Cited by 503
Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV
Lokugamage, K. G., Hage, A., de Vries, M., Valero-Jimenez, A. M., Schindewolf, C., Dittmann, M., Rajsbaum, R., & Menachery, V. D. (2020) · Journal of Virology · doi:10.1128/jvi.01410-20 · Cited by 503
Self-citationDysregulation of type I interferon responses in COVID-19
Acharya, D., Liu, G., & Gack, M. U. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0346-x · Cited by 454
Antiviral activities of type I interferons to SARS-CoV-2 infection
Mantlo, E., Bukreyeva, N., Maruyama, J., Paessler, S., & Huang, C. (2020) · Antiviral Research · doi:10.1016/j.antiviral.2020.104811 · Cited by 430
Narayanan, K., Huang, C., Lokugamage, K. G., Kamitani, W., Ikegami, T., Tseng, C.-T. K., & Makino, S. (2008) · Journal of Virology · doi:10.1128/jvi.02472-07 · Cited by 421
SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon
Totura, A. L., & Baric, R. S. (2012) · Current Opinion in Virology · doi:10.1016/j.coviro.2012.04.004 · Cited by 420
Kamitani, W., Narayanan, K., Huang, C., Lokugamage, K. G., Ikegami, T., Ito, N., Kubo, H., & Makino, S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603144103 · Cited by 418
A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein
Kamitani, W., Huang, C., Narayanan, K., Lokugamage, K. G., & Makino, S. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1680 · Cited by 410
Frieman, M. B., Ratia, K. M., Johnston, R. E., Mesecar, A. D., & Baric, R. S. (2009) · Journal of Virology · doi:10.1128/jvi.02220-08 · Cited by 371
Huang, C., Lokugamage, K. G., Rozovics, J. M., Narayanan, K., Semler, B. L., & Makino, S. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002433 · Cited by 353
An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction
Xia, H., Luo, H., Shan, C., Muruato, A. E., Nunes, B. T. D., Medeiros, D. B. D. A., Zou, J., Xie, X., Giraldo, M. I., Vasconcelos, P. F. D. C., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02816-2 · Cited by 316
Self-citationTranscriptional regulation by STAT1 and STAT2 in the interferon JAK-STAT pathway
Au-Yeung, N., Mandhana, R., & Horvath, C. M. (2013) · JAK-STAT · doi:10.4161/jkst.23931 · Cited by 307
Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response
Kindler, E., Thiel, V., & Weber, F. (2016) · Advances in virus research · doi:10.1016/bs.aivir.2016.08.006 · Cited by 296
Hu, Y., Li, W., Gao, T., Cui, Y., Jin, Y., Li, P., Ma, Q., Liu, X. E., & Cao, C. (2017) · Journal of Virology · doi:10.1128/jvi.02143-16 · Cited by 294
Siu, K., Kok, K., Ng, M.-H. J., Poon, V. K., Yuen, K., Zheng, B.-J., & Jin, D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.008227 · Cited by 276
Xie, X., Muruato, A. E., Zhang, X., Lokugamage, K. G., Fontes-Garfias, C. R., Zou, J., Liu, J., Ren, P., Balakrishnan, M., Cihlář, T., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19055-7 · Cited by 216
Self-citationType I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoVPreprint
Lokugamage, K. G., Hage, A., de Vries, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.07.982264 · Cited by 189
Envelope protein ubiquitination drives entry and pathogenesis of Zika virus
Giraldo, M. I., Xia, H., Aguilera-Aguirre, L., Hage, A., van Tol, S., Shan, C., Xie, X., Sturdevant, G. L., Robertson, S. J., McNally, K. L., et al. (2020) · Nature · doi:10.1038/s41586-020-2457-8 · Cited by 164
Self-citationOtsuka, M., Kato, N., Moriyama, M., Taniguchi, H., Wang, Y., Dharel, N., Kawabe, T., & Omata, M. (2005) · Hepatology · doi:10.1002/hep.20666 · Cited by 129
Bharaj, P., Wang, Y. E., Dawes, B. E., Yun, T., Park, A., Yen, B. C., Basler, C. F., Freiberg, A. N., Lee, B., & Rajsbaum, R. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005880 · Cited by 115
Self-citationCai, Z., Zhang, M., Tang, Z., Zhang, Q., Ye, J., Xiong, T.-C., Zhang, Z., & Zhong, B. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191174 · Cited by 84
Niemeyer, D., Mösbauer, K., Klein, E. M., Sieberg, A., Mettelman, R. C., Mielech, A. M., Dijkman, R., Baker, S. C., Drosten, C., & Müller, M. A. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007296 · Cited by 73
Dedeurwaerder, A., Olyslaegers, D. A. J., Desmarets, L. M. B., Roukaerts, I. D. M., Theuns, S., & Nauwynck, H. (2013) · Journal of General Virology · doi:10.1099/vir.0.058743-0 · Cited by 60
Schoggins, J. W., Wilson, S. J., Panis, M., Murphy, M. Y., Jones, C. T., Bieniasz, P. D., & Rice, C. M. (2015) · Nature · doi:10.1038/nature14554 · Cited by 44
Xie, X., Muruato, A. E., Zhang, X., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.22.165712 · Cited by 41
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- Lokugamage, 2020, SARS-CoV-2 is sensitive to type I interferon pretreatment, bioRxiv
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“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…”
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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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