AHR signaling is induced by infection with coronaviruses.
AHR signaling is induced by infection with coronaviruses.
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DOI：
10.1038/s41467-021-25412-x
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发表时间：
2021-08-26
影响因子：
16.6
通讯作者：
Quintana FJ
中科院分区：
文献类型：
--
作者：
Giovannoni F;Li Z;Remes-Lenicov F;Dávola ME;Elizalde M;Paletta A;Ashkar AA;Mossman KL;Dugour AV;Figueroa JM;Barquero AA;Ceballos A;Garcia CC;Quintana FJ
人类感染冠状病毒通常与呼吸道疾病有关，其严重程度从轻微到危及生命的呼吸衰竭不等。芳烃受体（AHR）最近被确定为寨卡病毒和登革热病毒的宿主因子； AHR 拮抗剂可增强抗病毒免疫力，降低病毒滴度并改善寨卡病毒引起的体内病理。在这里，我们报告说，AHR 是由不同冠状病毒感染激活的，可能会影响抗病毒免疫和肺上皮细胞。事实上，对肺组织的单细胞 RNA-seq 分析检测到 AHR 和 AHR 转录靶标的表达增加，表明来自 COVID-19 患者的 SARS-CoV-2 感染的上皮细胞中 AHR 信号激活。此外，我们检测到 SARS-CoV-2 感染患者的 AHR 表达与病毒载量之间存在关联。最后，我们发现 AHR 的药理学抑制作用抑制了普通感冒的病原体之一 HCoV-229E 和 COVID-19 大流行的病原体 SARS-CoV-2 的体外复制。总而言之，这些发现表明 AHR 激活是冠状病毒用来逃避抗病毒免疫和促进病毒复制的常见策略，这也可能导致肺部病理学。未来的研究应进一步评估 AHR 作为宿主定向抗病毒治疗靶点的潜力。 RNA 病毒，例如寨卡病毒和登革热病毒，会激活芳基碳氢化合物受体 (AHR) 信号传导以限制抗病毒反应。在这里，作者报告说，冠状病毒也会激活 AHR 信号传导，可能使它们逃避免疫反应，并表明 AHR 拮抗作用限制了 SARS-CoV-2 的体外复制，这表明 AHR 可以成为抗病毒治疗的目标。
Coronavirus infection in humans is usually associated to respiratory tract illnesses, ranging in severity from mild to life-threatening respiratory failure. The aryl hydrocarbon receptor (AHR) was recently identified as a host factor for Zika and dengue viruses; AHR antagonists boost antiviral immunity, decrease viral titers and ameliorate Zika-induced pathology in vivo. Here we report that AHR is activated by infection with different coronaviruses, potentially impacting antiviral immunity and lung epithelial cells. Indeed, the analysis of single-cell RNA-seq from lung tissue detected increased expression of AHR and AHR transcriptional targets, suggesting AHR signaling activation in SARS-CoV-2-infected epithelial cells from COVID-19 patients. Moreover, we detected an association between AHR expression and viral load in SARS-CoV-2 infected patients. Finally, we found that the pharmacological inhibition of AHR suppressed the replication in vitro of one of the causative agents of the common cold, HCoV-229E, and the causative agent of the COVID-19 pandemic, SARS-CoV-2. Taken together, these findings suggest that AHR activation is a common strategy used by coronaviruses to evade antiviral immunity and promote viral replication, which may also contribute to lung pathology. Future studies should further evaluate the potential of AHR as a target for host-directed antiviral therapy. RNA viruses, such as Zika and Dengue, activate the aryl hydrocarbon receptor (AHR) signaling to restrict the antiviral response. Here, the authors report that coronaviruses also activate AHR signaling, potentially allowing them to escape the immune response, and show that AHR antagonism limits SARS-CoV-2 replication in vitro, suggesting that AHR could be targeted for antiviral therapy.
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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
DOI：
10.1038/nrd.2017.162
发表时间：
2018-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Kaufmann SHE;Dorhoi A;Hotchkiss RS;Bartenschlager R
通讯作者：
Bartenschlager R
影响因子：
25
作者：
Giovannoni F;Bosch I;Polonio CM;Torti MF;Wheeler MA;Li Z;Romorini L;Rodriguez Varela MS;Rothhammer V;Barroso A;Tjon EC;Sanmarco LM;Takenaka MC;Modaresi SMS;Gutiérrez-Vázquez C;Zanluqui NG;Dos Santos NB;Munhoz CD;Wang Z;Damonte EB;Sherr D;Gehrke L;Peron JPS;Garcia CC;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
30.5
作者：
Galani, Ioanna-Evdokia;Rovina, Nikoletta;Andreakos, Evangelos
通讯作者：
Andreakos, Evangelos
影响因子：
15.3
作者：
Israelow, Benjamin;Song, Eric;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko