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Transcriptional and proteomic insights into the host response in fatal COVID-19 cases
Wu, Meng; Chen, Yaobing4; Xia, Han3,5; Wang, Changli6; Tan, Chin Yee1; Cai, Xunhui2; Liu, Yufeng2,7; Ji, Fenghu2,7; Xiong, Peng2,7; Liu, Ran
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2020-11-10
卷号117期号:45页码:28336-28343
关键词COVID-19 SARS-CoV-2 neutrophil fibrosis NETosis
ISSN号0027-8424
DOI10.1073/pnas.2018030117
通讯作者Liu, Liang(liuliang@mail.tjmu.du.cn) ; Wang, Guoping(wanggp@hust.edu.cn) ; Surana, Neeraj K.(neil.surana@duke.edu) ; Xia, Tian(tianxia@hust.edu.cn) ; Kasper, Dennis L.(dennis_kasper@hms.harvard.edu)
英文摘要Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.
资助项目Clinical Foundation of Tongji Hospital[XXGZBDYJ010] ; Ministry of Science and Technology of P. R. China Plan[2020YFC0844700] ; National Natural Science Foundation of China[61571202] ; NIH/National Institute of Allergy and Infectious Diseases[R01AI148273] ; National University of Singapore Development Grant
WOS关键词NEUTROPHIL EXTRACELLULAR TRAPS ; READ ALIGNMENT ; LUNG
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATL ACAD SCIENCES
WOS记录号WOS:000590745300016
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/292660]  
专题中国科学院上海药物研究所
通讯作者Liu, Liang; Wang, Guoping; Surana, Neeraj K.; Xia, Tian; Kasper, Dennis L.
作者单位1.Duke Univ, Dept Pediat, Sch Med, Durham, NC 27710 USA
2.Duke Univ, Dept Mol Genet & Microbiol, Sch Med, Durham, NC 27710 USA
3.Hugobiotech Co Ltd, Dept Res & Dev, Beijing 100000, Peoples R China
4.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Inst Pathol, Wuhan 430074, Peoples R China
5.Xi An Jiao Tong Univ, Fac Elect & Informat Engn, Sch Automat Sci & Engn, Xian 710049, Peoples R China
6.Huazhong Univ Sci & Technol, Sch Basic Med, Tongji Med Coll, Dept Pathol, Wuhan 430074, Peoples R China
7.Huazhong Univ Sci & Technol, Inst Artificial Intelligence, Wuhan 430074, Peoples R China
8.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pathol, Wuhan 430030, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
10.Baylor Coll Med, Dept Med, Houston, TX 77030 USA
推荐引用方式
GB/T 7714
Wu, Meng,Chen, Yaobing,Xia, Han,et al. Transcriptional and proteomic insights into the host response in fatal COVID-19 cases[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2020,117(45):28336-28343.
APA Wu, Meng.,Chen, Yaobing.,Xia, Han.,Wang, Changli.,Tan, Chin Yee.,...&Kasper, Dennis L..(2020).Transcriptional and proteomic insights into the host response in fatal COVID-19 cases.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,117(45),28336-28343.
MLA Wu, Meng,et al."Transcriptional and proteomic insights into the host response in fatal COVID-19 cases".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117.45(2020):28336-28343.
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