2. Academic Validation
  3. MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells

MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells

  • Cell Rep. 2021 Jan 12;34(2):108628. doi: 10.1016/j.celrep.2020.108628.
Xin Yin 1,  Laura Riva 2,  Yuan Pu 2,  Laura Martin-Sancho 2,  Jun Kanamune 3,  Yuki Yamamoto 3,  Kouji Sakai 4,  Shimpei Gotoh 3,  Lisa Miorin 5,  Paul D De Jesus 2,  Chih-Cheng Yang 6,  Kristina M Herbert 2,  Sunnie Yoh 2,  Judd F Hultquist 7,  Adolfo García-Sastre 8,  Sumit K Chanda 9
Affiliations

Affiliations

  • 1 Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, P.R. China.
  • 2 Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • 3 Department of Drug Discovery for Lung Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
  • 4 Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • 5 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 6 Functional Genomics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • 7 Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60201, USA.
  • 8 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 9 Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: schanda@sbpdiscovery.org.
PMID: 33440148 DOI: 10.1016/j.celrep.2020.108628
Abstract

Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity. Yet the molecular events that underlie cellular recognition and response to SARS-CoV-2 Infection remain to be elucidated. Here, we find that SARS-CoV-2 replication induces a delayed interferon (IFN) response in lung epithelial cells. By screening 16 putative sensors involved in sensing of RNA virus Infection, we found that MDA5 and LGP2 primarily regulate IFN induction in response to SARS-CoV-2 Infection. Further analyses revealed that viral intermediates specifically activate the IFN response through MDA5-mediated sensing. Additionally, we find that IRF3, IRF5, and NF-κB/p65 are the key transcription factors regulating the IFN response during SARS-CoV-2 Infection. In summary, these findings provide critical insights into the molecular basis of the innate immune recognition and signaling response to SARS-CoV-2.

Keywords

IRF3; IRF5; MDA5; NF-κB/p65; SARS-CoV-2; interferon; lung epithelial cells.

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