Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

被引:2996
作者
Blanco-Melo, Daniel [1 ,2 ]
Nilsson-Payant, Benjamin E. [1 ,2 ]
Liu, Wen-Chun [1 ,3 ]
Uhl, Skyler [1 ,2 ]
Hoagland, Daisy [1 ,2 ]
Moller, Rasmus [1 ,2 ]
Jordan, Tristan X. [1 ,2 ]
Oishi, Kohei [1 ,2 ]
Panis, Maryline [1 ,2 ]
Sachs, David [4 ]
Wang, Taia T. [5 ,6 ,7 ]
Schwartz, Robert E. [8 ]
Lim, Jean K. [1 ]
Albrecht, Randy A. [1 ,3 ]
tenOever, Benjamin R. [1 ,2 ,3 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Virus Engn Ctr Therapeut & Res, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA
[4] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
[5] Stanford Univ, Dept Med, Sch Med, Div Infect Dis, Stanford, CA 94305 USA
[6] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
[7] Chan Zuckerberg Biohub, San Francisco, CA USA
[8] Weill Cornell Med, Div Gastroenterol & Hepatol, Dept Med, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
INTERFERON; CORONAVIRUS; SARS; TRANSMISSION; PATHOGENESIS; INFECTION; PROTEIN; CELLS;
D O I
10.1016/j.cell.2020.04.026
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. Wepropose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.
引用
收藏
页码:1036 / +
页数:19
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