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Chen X, Saccon E, Appelberg KS, et al. Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells. Cell Death Discov. 2021;7(1):114doi: 10.1038/s41420-021-00487-z.
Chen, X., Saccon, E., Appelberg, K. S., Mikaeloff, F., Rodriguez, J. E., Vinhas, B. S., Frisan, T., Végvári, �. �., Mirazimi, A., Neogi, U., & Gupta, S. (2021). Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells. Cell death discovery, 7(1), 114. https://doi.org/10.1038/s41420-021-00487-z
Chen, Xi, et al. "Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells." Cell death discovery vol. 7,1 (2021): 114. doi: https://doi.org/10.1038/s41420-021-00487-z
Chen X, Saccon E, Appelberg KS, Mikaeloff F, Rodriguez JE, Vinhas BS, Frisan T, Végvári Á, Mirazimi A, Neogi U, Gupta S. Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells. Cell Death Discov. 2021 May 18;7(1):114. doi: 10.1038/s41420-021-00487-z. PMID: 34006825; PMCID: PMC8129603.
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Cell Death Discov. 2021 May 18;7(1):114. doi: 10.1038/s41420-021-00487-z.

Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells.

Cell death discovery

Xi Chen, Elisa Saccon, K Sofia Appelberg, Flora Mikaeloff, Jimmy Esneider Rodriguez, Beatriz Sá Vinhas, Teresa Frisan, Ákos Végvári, Ali Mirazimi, Ujjwal Neogi, Soham Gupta

Affiliations

  1. Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.
  2. Public Health Agency of Sweden, Solna, Sweden.
  3. Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  4. Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
  5. Manipal Center for Virus Research, Manipal University, Manipal, India.
  6. Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden. [email protected].

PMID: 34006825 PMCID: PMC8129603 DOI: 10.1038/s41420-021-00487-z

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has caused a global health emergency. A key feature of COVID-19 is dysregulated interferon-response. Type-I interferon (IFN-I) is one of the earliest antiviral innate immune responses following viral infection and plays a significant role in the pathogenesis of SARS-CoV-2. In this study, using a proteomics-based approach, we identified that SARS-CoV-2 infection induces delayed and dysregulated IFN-I signaling in Huh7 cells. We demonstrate that SARS-CoV-2 is able to inhibit RIG-I mediated IFN-β production. Our results also confirm the recent findings that IFN-I pretreatment is able to reduce the susceptibility of Huh7 cells to SARS-CoV-2, but not post-treatment. Moreover, senescent Huh7 cells, in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection, and the virus effectively inhibited IFIT1 in these cells. Finally, proteomic comparison between SARS-CoV-2, SARS-CoV, and MERS-CoV revealed a distinct differential regulatory signature of interferon-related proteins emphasizing that therapeutic strategies based on observations in SARS-CoV and MERS-CoV should be used with caution. Our findings provide a better understanding of SARS-CoV-2 regulation of cellular interferon response and a perspective on its use as a treatment. Investigation of different interferon-stimulated genes and their role in the inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.

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