Comparison of the pathogenesis of SARS-CoV-2 infection in K18-hACE2 mouse and Syrian golden hamster models

被引：22

作者：

Jeong, Haengdueng ^{[1
]}

Lee, Youn Woo ^{[2
]}

Park, In Ho ^{[1
,3
]}

Noh, Hyuna ^{[4
]}

Kim, Sung-Hee

Kim, Jiseon ^{[1
]}

Jeon, Donghun ^{[1
]}

Jang, Hui Jeong ^{[2
]}

Oh, Jooyeon ^{[5
]}

On, Dain ^{[4
,6
]}

Uhm, Chanyang ^{[1
]}

Cho, Kyungrae ^{[1
]}

Oh, Heeju ^{[1
]}

Yoon, Suhyeon

Seo, Jung Seon ^{[1
]}

Kim, Jeong Jin ^{[1
]}

Seok, Sang-Hyuk ^{[7
,8
]}

Lee, Yu Jin ^{[7
]}

Hong, Seung-Min

An, Se-Hee

Kim, Seo Yeon ^{[9
]}

Kim, Young Been ^{[9
]}

Hwang, Ji-Yeon ^{[9
]}

Lee, Hyo-Jung ^{[10
]}

Kim, Hong Bin ^{[11
]}

Jeong, Dae Gwin ^{[12
]}

Song, Daesub ^{[13
]}

Song, Manki ^{[14
]}

Park, Man-Seong ^{[15
]}

Choi, Kang-Seuk ^{[8
]}

Park, Jun Won ^{[7
]}

Seo, Jun-Young ^{[1
]}

Yun, Jun-Won ^{[16
]}

Shin, Jeon-Soo ^{[1
,3
,5
]}

Lee, Ho-Young ^{[2
,17
]}

Nam, Ki Taek ^{[1
]}

Seong, Je Kyung ^{[4
,18
,19
]}

机构：

[1] Yonsei Univ, Severance Biomed Sci Inst, Brain Korea 21 FOUR Project Med Sci, Coll Med, Seoul 03722, South Korea

[2] Seoul Natl Univ, Bundang Hosp, Dept Nucl Med, Seongnam 13488, South Korea

[3] Yonsei Univ, Inst Immunol & Immunol Dis, Coll Med, Seoul 03722, South Korea

[4] Seoul Natl Univ, Korea Mouse Phenotyping Ctr, Seoul 08826, South Korea

[5] Yonsei Univ, Coll Med, Dept Microbiol, Seoul 03722, South Korea

[6] Seoul Natl Univ, Res Inst Vet Sci, Coll Vet Med, Brain Korea 21 FOUR Program Creat Vet Sci Res ,Lab, Seoul 08826, South Korea

[7] Kangwon Natl Univ, Coll Biomed Sci, Div Biomed Convergence, Chunchon 24341, South Korea

[8] Seoul Natl Univ, Res Inst Vet Sci, Coll Vet Med, Brain Korea21 FOUR Program Vet Sci, Seoul 08826, South Korea

[9] Seoul Natl Univ, Preclin Res Ctr, Seongnam 13488, South Korea

[10] Seoul Natl Univ, Dept Periodontol, Sect Dent, Bundang Hosp, Seongnam 13620, South Korea

[11] Seoul Natl Univ, Coll Med, Bundang Hosp, Dept Internal Med, Seongnam 13620, South Korea

[12] Korea Res Inst Biosci & Biotechnol, Bionanotechnol Res Ctr, Daejeon 34141, South Korea

[13] Seoul Natl Univ, Res Inst Vet Sci, Coll Vet Med, Dept Vet Med Virol Lab, Seoul 08826, South Korea

[14] Int Vaccine Inst, Sci Unit, Seoul 08826, South Korea

[15] Korea Univ, Inst Viral Dis, Biosafety Ctr, Dept Microbiol,Coll Med, Seoul 02841, South Korea

[16] Seoul Natl Univ, Coll Vet Med, Lab Vet Toxicol, Seoul 08826, South Korea

[17] Seoul Natl Univ, Coll Med, Dept Nucl Med, Seoul 03080, South Korea

[18] Seoul Natl Univ, BIOMAX Inst, Seoul 08826, South Korea

[19] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 08826, South Korea

来源：

DISEASE MODELS & MECHANISMS | 2022年 / 15卷 / 11期

基金：

新加坡国家研究基金会;

关键词：

SARS-CoV-2; Syrian golden hamster; K18-hACE2; mice; COVID-19; ACE2; SARS;

D O I：

10.1242/dmm.049632

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, causes life-threatening disease. This novel coronavirus enters host cells via the respiratory tract, promoting the formation of severe pulmonary lesions and systemic disease. Few animal models can simulate the clinical signs and pathology of COVID-19 patients. Diverse preclinical studies using K18-hACE2 mice and Syrian golden hamsters, which are highly permissive to SARS-CoV-2 in the respiratory tract, are emerging; however, the systemic pathogenesis and cellular tropism of these models remain obscure. We intranasally infected K18-hACE2 mice and Syrian golden hamsters with SARS-CoV-2, and compared the clinical features, pathogenesis, cellular tropism and infiltrated immune-cell subsets. In K18-hACE2 mice, SARS-CoV-2 persistently replicated in alveolar cells and caused pulmonary and extrapulmonary disease, resulting in fatal outcomes. Conversely, in Syrian golden hamsters, transient SARS-CoV-2 infection in bronchial cells caused reversible pulmonary disease, without mortality. Our findings provide comprehensive insights into the pathogenic spectrum of COVID-19 using preclinical models.

引用

页数：13

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