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

Cell Reports
Xin YinSumit K Chanda

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.

References

Apr 25, 2007·Virus Research·Matthew FriemanRalph Baric
Jan 6, 2009·Immunological Reviews·Osamu Takeuchi, Shizuo Akira
Apr 15, 2011·Genes and Immunity·S NingG N Barber
Jan 20, 2012·Journal of Virology·Søren Jensen, Allan Randrup Thomsen
Aug 8, 2014·Frontiers in Immunology·Stephanie ReikineYorgo Modis
Feb 24, 2015·Trends in Immunology·Hans-Heinrich HoffmannCharles M Rice
Nov 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yi-Hsin FanRavit Arav-Boger
Aug 12, 2017·Cell Host & Microbe·Adolfo García-Sastre
Oct 3, 2017·Nature Methods·Yuki YamamotoMichiaki Mishima
Nov 22, 2017·Signal Transduction and Targeted Therapy·Ting LiuShao-Cong Sun
Mar 25, 2019·International Journal of Molecular Sciences·Megan L StaniferSteeve Boulant
Apr 18, 2019·Immunity·Helen M LazearMichael S Diamond
Jul 30, 2019·The Journal of Clinical Investigation·Rudragouda ChannappanavarStanley Perlman
Oct 3, 2019·Science Signaling·Raul Y Sanchez DavidAnastassia V Komarova
Dec 13, 2019·Experimental & Molecular Medicine·Hyun-Cheol LeeJong-Soo Lee
Mar 15, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiao Man WuMing Xian Chang
Mar 20, 2020·Cell & Bioscience·Kit-San YuenDong-Yan Jin
Mar 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Matthew HackbartSusan C Baker
Apr 3, 2020·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Nicola PetrosilloEskild Petersen
Apr 11, 2020·The New England Journal of Medicine·Jonathan GreinTimothy Flanigan
May 3, 2020·Science·Mart M LamersHans Clevers
May 15, 2020·Cell Host & Microbe·Zhuo ZhouJianwei Wang
Jun 12, 2020·Immunologic Research·Domenico BirraPaolo Moscato
Jun 27, 2020·The Journal of Biological Chemistry·Ulrike FelgenhauerFriedemann Weber
Jul 12, 2020·Nature Microbiology·Chantal B F VogelsNathan D Grubaugh
Jul 20, 2020·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Bo WangTiejun Wang
Jul 28, 2020·Nature·Carolina LucasAkiko Iwasaki
Jul 29, 2020·Journal of Infection and Public Health·Mohammad Asaduzzaman ChowdhuryAshraful Alam
Aug 1, 2020·Nature Communications·Xiaobo LeiJianwei Wang

❮ Previous
Next ❯

Citations

May 1, 2021·Molecular Cell·Laura Martin-SanchoSumit K Chanda
May 13, 2021·Nature Immunology·Taisho YamadaAkinori Takaoka
Jun 12, 2021·Communications Biology·Matthieu SimeoniDavid Gatfield
Jun 11, 2021·Frontiers in Research Metrics and Analytics·Mengjia WuJie Lu
Jun 16, 2021·The Journal of Experimental Medicine·Nagarjuna R CheemarlaEllen F Foxman
Jun 24, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thomas KehrerLisa Miorin
Jun 29, 2021·Advanced Therapeutics·Haodong GuoFangfang Zhou

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
nuclear translocation
gene knockout
Assay

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.