Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice

被引：287

作者：

Oladunni, Fatai S. ^{[1
]}

Park, Jun-Gyu ^{[1
]}

Pino, Paula A. ^{[1
]}

Gonzalez, Olga ^{[1
]}

Akhter, Anwari ^{[1
]}

Allue-Guardia, Anna ^{[1
]}

Olmo-Fontanez, Angelica ^{[1
,2
]}

Gautam, Shalini ^{[1
]}

Garcia-Vilanova, Andreu ^{[1
]}

Ye, Chengjin ^{[1
]}

Chiem, Kevin ^{[1
,2
]}

Headley, Colwyn ^{[1
]}

Dwivedi, Varun ^{[1
]}

Parodi, Laura M. ^{[1
]}

Alfson, Kendra J. ^{[1
]}

Staples, Hilary M. ^{[1
]}

Schami, Alyssa ^{[1
,2
]}

Garcia, Juan, I ^{[1
]}

Whigham, Alison ^{[1
]}

Platt, Roy Neal, II ^{[1
]}

Gazi, Michal ^{[1
]}

Martinez, Jesse ^{[1
]}

Chuba, Colin ^{[1
]}

Earley, Stephanie ^{[1
]}

Rodriguez, Oscar H. ^{[1
]}

Mdaki, Stephanie Davis ^{[1
]}

Kavelish, Katrina N. ^{[1
]}

Escalona, Renee ^{[1
]}

Hallam, Cory R. A. ^{[1
]}

Christie, Corbett ^{[1
]}

Patterson, Jean L. ^{[1
]}

Anderson, Tim J. C. ^{[1
]}

Carrion, Ricardo, Jr. ^{[1
]}

Dick, Edward J., Jr. ^{[1
]}

Hall-Ursone, Shannan ^{[1
]}

Schlesinger, Larry S. ^{[1
]}

Alvarez, Xavier ^{[1
]}

Kaushal, Deepak ^{[1
]}

Giavedoni, Luis D. ^{[1
]}

Turner, Joanne ^{[1
]}

Martinez-Sobrido, Luis ^{[1
]}

Torrelles, Jordi B. ^{[1
]}

机构：

[1] Texas Biomed Res Inst, San Antonio, TX 78227 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Integrated Biomed Sci Program, San Antonio, TX 78229 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

CYTOKINE STORM;

D O I：

10.1038/s41467-020-19891-7

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：

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

引用

页数：17

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