STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters

被引：187

作者：

Boudewijns, Robbert ^{[1
,2
,3
]}

Thibaut, Hendrik Jan ^{[1
,3
,4
]}

Kaptein, Suzanne J. F. ^{[1
,3
]}

Li, Rong ^{[5
]}

Vergote, Valentijn ^{[1
,6
,7
]}

Seldeslachts, Laura ^{[8
]}

Van Weyenbergh, Johan ^{[6
]}

De Keyzer, Carolien ^{[1
,2
,3
]}

Bervoets, Lindsey ^{[1
,3
]}

Sharma, Sapna ^{[1
,2
,3
]}

Liesenborghs, Laurens ^{[1
,2
,3
]}

Ma, Ji ^{[1
,2
,3
]}

Jansen, Sander ^{[1
,2
,3
]}

Van Looveren, Dominique ^{[1
,3
,4
]}

Vercruysse, Thomas ^{[1
,3
,4
]}

Wang, Xinyu ^{[1
,2
,3
]}

Jochmans, Dirk ^{[1
,2
,3
]}

Martens, Erik ^{[9
]}

Roose, Kenny ^{[10
,11
]}

De Vlieger, Dorien ^{[10
,11
]}

Schepens, Bert ^{[10
,11
]}

Van Buyten, Tina ^{[1
,3
]}

Jacobs, Sofie ^{[1
,3
]}

Liu, Yanan ^{[5
]}

Marti-Carreras, Joan ^{[6
,7
]}

Vanmechelen, Bert ^{[6
,7
]}

Wawina-Bokalanga, Tony ^{[6
,7
]}

Delang, Leen ^{[1
,3
]}

Rocha-Pereira, Joana ^{[1
,3
]}

Coelmont, Lotte ^{[1
,2
,3
]}

Chiu, Winston ^{[1
,3
]}

Leyssen, Pieter ^{[1
,3
]}

Heylen, Elisabeth ^{[1
,3
]}

Schols, Dominique ^{[1
]}

Wang, Lanjiao ^{[1
,3
]}

Close, Lila ^{[6
,12
]}

Matthijnssens, Jelle ^{[6
,12
]}

Van Ranst, Marc ^{[6
,13
,14
,15
]}

Compernolle, Veerle ^{[16
,17
]}

SchrammH, Georg ^{[18
,19
,20
]}

Van Laere, Koen ^{[18
,19
,20
]}

Saelens, Xavier ^{[10
,11
]}

Callewaert, Nico ^{[10
,11
]}

Opdenakker, Ghislain ^{[9
]}

Maes, Piet ^{[6
,7
]}

Weynand, Birgit ^{[21
,22
]}

Cawthorne, Christopher ^{[18
,19
]}

Vande Velde, Greetje ^{[8
]}

Wang, Zhongde ^{[5
]}

Neyts, Johan ^{[1
,2
,3
]}

机构：

[1] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Rega Inst, Lab Virol & Chemotherapy, B-3000 Leuven, Belgium

[2] Mol Vaccinol & Vaccine Discovery Grp, Leuven, Belgium

[3] Global Virus Network, GVN, Baltimore, MD 21201 USA

[4] Translat Platform Virol & Chemotherapy, Leuven, Belgium

[5] Utah State Univ, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA

[6] Katholieke Univ Leuven, Lab Clin & Epidemiol Virol, Rega Inst, Dept Microbiol Immunol & Transplantat, B-3000 Leuven, Belgium

[7] Zoonot Infect Dis Unit, Leuven, Belgium

[8] Katholieke Univ Leuven, Dept Imaging & Pathol, Biomed MRI & MoSAIC, B-3000 Leuven, Belgium

[9] Katholieke Univ Leuven, Immun & Inflammat Res Grp, Immunobiol Unit, Rega Inst,Dept Microbiol Immunol & Transplantat, B-3000 Leuven, Belgium

[10] VIB, VIB UGent Ctr Med Biotechnol, B-9052 Ghent, Belgium

[11] Univ Ghent, Dept Biochem & Microbiol, B-9052 Ghent, Belgium

[12] Lab Viral Metagen, Leuven, Belgium

[13] Katholieke Univ Leuven, Dept Lab Med, Univ Hosp Leuven, B-3000 Leuven, Belgium

[14] Natl Reference Ctr Resp Pathogens & Enteroviruses, B-3000 Leuven, Belgium

[15] Leuven Univ Vaccinol Ctr LUVAC, B-3000 Leuven, Belgium

[16] Belgian Red Cross Flanders, Blood Serv, Mechelen, Belgium

[17] Univ Ghent, Fac Med & Hlth Sci, Ghent, Belgium

[18] Katholieke Univ Leuven, Dept Imaging & Pathol Nucl Med & Mol Imaging, B-3000 Leuven, Belgium

[19] Katholieke Univ Leuven, MoSAIC, B-3000 Leuven, Belgium

[20] Univ Hosp Leuven, Div Nucl Med, B-3000 Leuven, Belgium

[21] Katholieke Univ Leuven, Dept Imaging & Pathol Translat Cell & Tissue Res, B-3000 Leuven, Belgium

[22] Div Translat Cell & Tissue Res, Leuven, Belgium

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; SAMPLE PREPARATION PROCEDURES; MODULAR APPROACH; I INTERFERON; MICE; SARS; COVID-19; PATHOGENESIS; MACROPHAGES; MODEL;

D O I：

10.1038/s41467-020-19684-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients. SARS-CoV-2 infection can result in severe lung inflammation and pathology, but host response remains incompletely understood. Here the authors show in Syrian hamsters that STAT2 signaling restricts systemic virus dissemination but also drives severe lung injury, playing a dual role in SARS-CoV-2 infection.

引用

页数：10

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