Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics.
Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics.
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DOI：
10.1084/jem.20210583
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发表时间：
2021-08-02
期刊：
影响因子：
--
通讯作者：
Foxman EF
中科院分区：
文献类型：
--
作者：
Cheemarla NR;Watkins TA;Mihaylova VT;Wang B;Zhao D;Wang G;Landry ML;Foxman EF
SARS-CoV-2在上呼吸道的复制启动感染并导致病毒传播。Cheemarla等人表明，动态的先天免疫反应可以在感染早期抑制病毒复制，并且最近接触鼻病毒可以加速先天防御并阻止病毒复制。SARS-CoV-2在上呼吸道的初始复制是建立感染所必需的，复制水平与病毒传播的可能性相关。在这里，我们研究了宿主先天免疫防御在限制早期SARS-CoV-2感染中的作用，使用转录组学和基于生物标志物的跟踪系列患者鼻咽样本和气道上皮类器官实验。SARS-CoV-2最初以指数方式复制，倍增时间为1.66小时，并在上呼吸道中诱导干扰素刺激基因（ISG），ISG随着病毒复制而上升，并在病毒载量开始下降时达到峰值。在SARS-CoV-2暴露前鼻病毒感染加速ISG反应并阻止SARS-CoV-2复制。相反，在SARS-CoV-2感染期间阻断ISG诱导增强了低感染剂量的病毒复制。这些结果表明，在SARS-CoV-2暴露时ISG介导的防御活性影响感染进展，并且由不同病毒诱导的异源抗病毒应答可以保护免受SARS-CoV-2的侵害。
SARS-CoV-2 replication in the upper respiratory tract initiates infection and leads to viral transmission. Cheemarla et al. show that a dynamic innate immune response can curtail viral replication early in infection, and that recent exposure to rhinovirus accelerates innate defenses and blocks viral replication. Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and the replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting early SARS-CoV-2 infection using transcriptomics and biomarker-based tracking in serial patient nasopharyngeal samples and experiments with airway epithelial organoids. SARS-CoV-2 initially replicated exponentially, with a doubling time of ∼6 h, and induced interferon-stimulated genes (ISGs) in the upper respiratory tract, which rose with viral replication and peaked just as viral load began to decline. Rhinovirus infection before SARS-CoV-2 exposure accelerated ISG responses and prevented SARS-CoV-2 replication. Conversely, blocking ISG induction during SARS-CoV-2 infection enhanced viral replication from a low infectious dose. These results show that the activity of ISG-mediated defenses at the time of SARS-CoV-2 exposure impacts infection progression and that the heterologous antiviral response induced by a different virus can protect against SARS-CoV-2.
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影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
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
影响因子：
10.5
作者：
Iwasaki A
通讯作者：
Iwasaki A
DOI：
10.1016/j.jcv.2009.03.008
发表时间：
2009-05
期刊：
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
影响因子：
--
作者：
Greer RM;McErlean P;Arden KE;Faux CE;Nitsche A;Lambert SB;Nissen MD;Sloots TP;Mackay IM
通讯作者：
Mackay IM
影响因子：
4.7
作者：
Anestad, Gabriel;Nordbo, Svein Arne
通讯作者：
Nordbo, Svein Arne