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Activation and evasion of type I interferon responses by SARS-CoV-2

Author

Listed:
  • Xiaobo Lei

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiaojing Dong

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ruiyi Ma

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wenjing Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xia Xiao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhongqin Tian

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Conghui Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ying Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Li Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lili Ren

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Fei Guo

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhendong Zhao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhuo Zhou

    (Peking University)

  • Zichun Xiang

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jianwei Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.

Suggested Citation

  • Xiaobo Lei & Xiaojing Dong & Ruiyi Ma & Wenjing Wang & Xia Xiao & Zhongqin Tian & Conghui Wang & Ying Wang & Li Li & Lili Ren & Fei Guo & Zhendong Zhao & Zhuo Zhou & Zichun Xiang & Jianwei Wang, 2020. "Activation and evasion of type I interferon responses by SARS-CoV-2," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17665-9
    DOI: 10.1038/s41467-020-17665-9
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    Cited by:

    1. Maritza Puray-Chavez & Jenna E. Eschbach & Ming Xia & Kyle M. LaPak & Qianzi Zhou & Ria Jasuja & Jiehong Pan & Jian Xu & Zixiang Zhou & Shawn Mohammed & Qibo Wang & Dana Q. Lawson & Sanja Djokic & Gao, 2024. "A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Xiaopan Gao & Huabin Tian & Kaixiang Zhu & Qing Li & Wei Hao & Linyue Wang & Bo Qin & Hongyu Deng & Sheng Cui, 2022. "Structural basis for Sarbecovirus ORF6 mediated blockage of nucleocytoplasmic transport," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Guoli Shi & Tiansheng Li & Kin Kui Lai & Reed F. Johnson & Jonathan W. Yewdell & Alex A. Compton, 2024. "Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Manon Venet & Margarida Sa Ribeiro & Elodie Décembre & Alicia Bellomo & Garima Joshi & Célia Nuovo & Marine Villard & David Cluet & Magali Perret & Rémi Pescamona & Helena Paidassi & Thierry Walzer & , 2023. "Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    5. Urszula Radzikowska & Andrzej Eljaszewicz & Ge Tan & Nino Stocker & Anja Heider & Patrick Westermann & Silvio Steiner & Anita Dreher & Paulina Wawrzyniak & Beate Rückert & Juan Rodriguez-Coira & Damir, 2023. "Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    6. Catherine F. Hatton & Rachel A. Botting & Maria Emilia Dueñas & Iram J. Haq & Bernard Verdon & Benjamin J. Thompson & Jarmila Stremenova Spegarova & Florian Gothe & Emily Stephenson & Aaron I. Gardner, 2021. "Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    7. Marziah Hashimi & T. Andrew Sebrell & Jodi F. Hedges & Deann Snyder & Katrina N. Lyon & Stephanie D. Byrum & Samuel G. Mackintosh & Dan Crowley & Michelle D. Cherne & David Skwarchuk & Amanda Robison , 2023. "Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Sung Hee Ko & Pierce Radecki & Frida Belinky & Jinal N. Bhiman & Susan Meiring & Jackie Kleynhans & Daniel Amoako & Vanessa Guerra Canedo & Margaret Lucas & Dikeledi Kekana & Neil Martinson & Limakats, 2024. "Rapid intra-host diversification and evolution of SARS-CoV-2 in advanced HIV infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Deanna M. Santer & Daniel Li & Yanal Ghosheh & Muhammad Atif Zahoor & Dhanvi Prajapati & Bettina E. Hansen & D. Lorne J. Tyrrell & Jordan J. Feld & Adam J. Gehring, 2022. "Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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