Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses

被引：43

作者：

Banerjee, Arinjay ^{[1
,2
,3
,21
]}

El-Sayes, Nader ^{[3
,4
]}

Budylowski, Patrick ^{[5
]}

Jacob, Rajesh Abraham ^{[1
,2
,3
]}

Richard, Daniel ^{[6
]}

Maan, Hassaan ^{[7
,8
]}

Aguiar, Jennifer A. ^{[9
]}

Demian, Wael L. ^{[1
,2
,3
]}

Baid, Kaushal ^{[3
,4
]}

D'Agostino, Michael R. ^{[2
,3
,4
]}

Ang, Jann Catherine ^{[2
,3
,4
]}

Murdza, Tetyana ^{[3
,4
]}

Tremblay, Benjamin J-M ^{[9
]}

Afkhami, Sam ^{[2
,3
,4
]}

Karimzadeh, Mehran ^{[7
]}

Irving, Aaron T. ^{[11
,12
]}

Yip, Lily ^{[13
]}

Ostrowski, Mario ^{[14
,15
]}

Hirota, Jeremy A. ^{[2
,16
,17
]}

Kozak, Robert ^{[13
,18
]}

Capellini, Terence D. ^{[6
]}

Miller, Matthew S. ^{[2
,3
,4
]}

Wang, Bo ^{[7
,8
,10
,18
]}

Mubareka, Samira ^{[13
,18
]}

McGeer, Allison J. ^{[19
,20
]}

McArthur, Andrew G. ^{[2
,4
]}

Doxey, Andrew C. ^{[2
,9
]}

Mossman, Karen ^{[1
,2
,3
]}

机构：

[1] McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada

[2] McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON L8S 4K1, Canada

[3] McMaster Univ, McMaster Immunol Res Ctr, Hamilton, ON L8S 4K1, Canada

[4] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8S 4K1, Canada

[5] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada

[6] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA

[7] Vector Inst Artificial Intelligence, Toronto, ON M5G 1M1, Canada

[8] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON M5G 2C4, Canada

[9] Univ Waterloo, Dept Biol, Waterloo, ON N2L 3G1, Canada

[10] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 2E4, Canada

[11] Zhejiang Univ, Univ Edinburgh Inst, Haining 314400, Zhejiang, Peoples R China

[12] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou 310027, Peoples R China

[13] Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada

[14] Univ Toronto, Dept Med, Toronto, ON M5S 3H2, Canada

[15] St Michaels Hosp, UnityHlth, Keenan Res Ctr Biomed Sci, Toronto, ON M5B 1W8, Canada

[16] McMaster Univ, Dept Med, Div Respirol, Hamilton, ON L8N 3Z5, Canada

[17] Univ British Columbia, Div Resp Med, Vancouver, BC V5Z 1M9, Canada

[18] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada

[19] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada

[20] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada

[21] Univ Saskatchewan, Dept Vet Microbiol, Vaccine & Infect Dis Org, Saskatoon, SK S7N 5E3, Canada

来源：

ISCIENCE | 2021年 / 24卷 / 05期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

EAST RESPIRATORY SYNDROME; PAPAIN-LIKE PROTEASE; HUMAN CYTOMEGALOVIRUS; GROWTH-FACTORS; CORONAVIRUS; REPLICATION; PATHWAY; EXPRESSION; SARS; 4A;

D O I：

10.1016/j.isci.2021.102477

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：

Type I interferons (IFNs) are our first line of defense against virus infection. Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent of IFN production is associated withmanifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wild-type SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are scarce. Here we demonstrate that SARS-CoV-2 infection induces a type I IFN response in vitro and inmoderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Furthermore, we show that physiological levels of IFNa detected in patients with moderate COVID-19 is sufficient to suppress SARS-CoV-2 replication in human airway cells.

引用

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