Interferon resistance of emerging SARS-CoV-2 variants.
Interferon resistance of emerging SARS-CoV-2 variants.
复制标题
DOI：
10.1073/pnas.2203760119
复制
发表时间：
2022-08-09
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
在短短两年多的时间里，SARS-CoV-2已经感染了5亿人，造成600多万人死亡。高感染率为病毒进化提供了大量机会，因为已经出现了具有增强的传播性、致病性和对中和抗体的抗性的变体。虽然很多焦点集中在刺突蛋白上，但在其他可能抑制干扰素的病毒蛋白中也检测到了突变，其中两种干扰素α2和IFNβ正在被重新用于COVID-19治疗。在这里，我们比较了不同的人干扰素对祖先和新出现的SARS-CoV-2变体的效力。我们的数据显示，SARS-CoV-2变异体的干扰素耐药性增加，这表明先天免疫在推动COVID-19大流行的下一阶段中发挥了重要但未被充分认识的作用。SARS-CoV-2变异株的出现增强了传播性、致病性和对疫苗的耐药性，这对遏制COVID-19大流行提出了紧迫的挑战。虽然增强病毒感染性或中和抗体逃避的刺突突变可能会驱动这些新变体的出现，但研究记录了干扰素应答在SARS-CoV-2感染早期控制中的关键作用，结合限制这些应答的病毒基因的存在，表明干扰素也可能影响SARS-CoV-2的进化。在这里，我们比较了17种不同的人干扰素对全球疫情期间采样的多种病毒谱系的效力，包括祖先和五种主要的关注变体，包括B.1.1.7（alpha），B.1.351（beta），P.1（gamma），B.1.617.2（delta）和B.1.1.529（omicron）谱系。我们的数据显示，相对于祖先分离株，SARS-CoV-2变异的关注表现出增加的干扰素耐药性，这表明先天免疫的逃避可能是一个重要的，持续的驱动力SARS-CoV-2进化。这些发现对新出现的变体的增加的传播性和/或致死性具有影响，并突出了可能在治疗早期感染中最成功的干扰素亚型。
In just over 2 years, SARS-CoV-2 has infected 500 million people, causing more than 6 million COVID-19 deaths. High infection rates have provided substantial opportunities for the virus to evolve, as variants with enhanced transmissibility, pathogenesis, and resistance to neutralizing antibodies have emerged. While much focus has centered on the Spike protein, mutations were also detected in other viral proteins that may inhibit the interferons, two of which, IFNα2 and IFNβ, are being repurposed for COVID-19 treatment. Here, we compared the potency of diverse human interferons against ancestral and emerging variants of SARS-CoV-2. Our data revealed increased interferon resistance in SARS-CoV-2 variants of concern, suggesting a significant but underappreciated role for innate immunity in driving the next phase of the COVID-19 pandemic. The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis, and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and five major variants of concern that include the B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta), and B.1.1.529 (omicron) lineages. Our data reveal that relative to ancestral isolates, SARS-CoV-2 variants of concern exhibited increased interferon resistance, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased transmissibility and/or lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.
登录
查看更多内容
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS
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：
56.9
作者：
Gonzalez-Reiche, Ana S.;Hernandez, Matthew M.;van Bakel, Harm
通讯作者：
van Bakel, Harm
影响因子：
16
作者：
Martin-Sancho L;Lewinski MK;Pache L;Stoneham CA;Yin X;Becker ME;Pratt D;Churas C;Rosenthal SB;Liu S;Weston S;De Jesus PD;O'Neill AM;Gounder AP;Nguyen C;Pu Y;Curry HM;Oom AL;Miorin L;Rodriguez-Frandsen A;Zheng F;Wu C;Xiong Y;Urbanowski M;Shaw ML;Chang MW;Benner C;Hope TJ;Frieman MB;García-Sastre A;Ideker T;Hultquist JF;Guatelli J;Chanda SK
通讯作者：
Chanda SK
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