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.
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DOI：
10.1016/j.celrep.2020.108628
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发表时间：
2021-01-12
期刊：
影响因子：
8.8
通讯作者：
Chanda SK
中科院分区：
文献类型：
--
作者：
Yin X;Riva L;Pu Y;Martin-Sancho L;Kanamune J;Yamamoto Y;Sakai K;Gotoh S;Miorin L;De Jesus PD;Yang CC;Herbert KM;Yoh S;Hultquist JF;García-Sastre A;Chanda SK
最近的研究描绘了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染患者的先天免疫特征，并表明细胞对病毒攻击的反应可能影响疾病的严重程度。然而，细胞识别和响应SARS-CoV-2感染的分子事件仍有待阐明。在这里，我们发现，SARS-CoV-2复制诱导延迟干扰素（IFN）反应在肺上皮细胞。通过筛选16个参与RNA病毒感染感知的推定传感器，我们发现MDA 5和LGP 2主要调节响应SARS-CoV-2感染的IFN诱导。进一步的分析表明，病毒中间体通过MDA 5介导的传感特异性激活IFN应答。此外，我们发现IRF 3、IRF 5和NF-κB/p65是调控SARS病毒感染过程中IFN应答的关键转录因子。总之，这些发现为SARS-CoV-2的先天免疫识别和信号应答的分子基础提供了重要的见解。先天免疫识别和对SARS-CoV-2感染的反应的分子事件仍然不清楚。Yin等人报道，SARS-CoV-2复制诱导延迟的干扰素（IFN）应答，该应答是通过MDA 5模式识别受体感知病毒RNA而触发的。
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. The molecular events that underlie innate immune recognition and response to SARS-CoV-2 infection remain unclear. Yin et al. report that SARS-CoV-2 replication induces a delayed interferon (IFN) response that is triggered by sensing of viral RNA through the MDA5 pattern recognition receptor.
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危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
病毒逃避干扰素的十种策略。
影响因子：
30.3
作者：
García-Sastre A
通讯作者：
García-Sastre A
影响因子：
16.8
作者：
Hoffmann HH;Schneider WM;Rice CM
通讯作者：
Rice CM
DOI：
10.1074/jbc.ac120.013788
发表时间：
2020-10-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Felgenhauer U;Schoen A;Gad HH;Hartmann R;Schaubmar AR;Failing K;Drosten C;Weber F
通讯作者：
Weber F
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans