Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

被引：430

作者：

Jiang, Ren-Di ^{[1
,2
]}

Liu, Mei-Qin ^{[1
,2
]}

Chen, Ying ^{[1
,2
]}

Shan, Chao ^{[1
]}

Zhou, Yi-Wu ^{[3
]}

Shen, Xu-Rui ^{[1
,2
]}

Li, Qian ^{[1
,2
]}

Zhang, Lei ^{[1
]}

Zhu, Yan ^{[1
]}

Si, Hao-Rui ^{[1
,2
]}

Wang, Qi ^{[1
]}

Min, Juan ^{[1
]}

Wang, Xi ^{[1
,2
]}

Zhang, Wei ^{[1
]}

Li, Bei ^{[1
]}

Zhang, Hua-Jun ^{[1
]}

Baric, Ralph S. ^{[4
]}

Zhou, Peng ^{[1
]}

Yang, Xing-Lou ^{[1
]}

Shi, Zheng-Li ^{[1
]}

机构：

[1] Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, CAS Key Lab Special Pathogens, Wuhan, Hubei, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Huazhong Univ Sci & Technol, Dept Forens Med, Tongji Med Coll, Wuhan, Hubei, Peoples R China

[4] Univ North Carolina, Chapel Hill, NC 27515 USA

来源：

CELL | 2020年 / 182卷 / 01期

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; CLINICAL CHARACTERISTICS; INFECTION; SARS; MODELS;

D O I：

10.1016/j.cell.2020.05.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.

引用

页码：50 / +

页数：17

共 50 条

[31] Origin and genomic characteristics of SARS-CoV-2 and its interaction with angiotensin converting enzyme type 2 receptors, focusing on the gastrointestinal tract [J].

Galanopoulos, Michail ;

Doukatas, Aris ;

Gazouli, Maria .

WORLD JOURNAL OF GASTROENTEROLOGY, 2020, 26 (41) :6335-6345

[32] Severity of SARS-COV-2 infection and angiotensin converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis [J].

Oscanoa, Teodoro J. ;

Vidal, Xavier ;

Carvajal, Alfonso ;

Amado, Jose ;

Romero-Ortuno, Roman .

ARTERIAL HYPERTENSION, 2020, 24 (03) :106-114

[33] In-silico Analysis of Angiotensin-converting Enzyme 2 (ACE2) of Livestock, Pet and Poultry Animals to Determine its Susceptibility to SARS-CoV-2 Infection [J].

Kumar, Aman ;

Panwar, Anil ;

Batra, Kanisht ;

De, Sachinandan ;

Maan, Sushila .

COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 2021, 24 (10) :1769-1783

[34] Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS-CoV) and its putative receptor, angiotensin-converting enzyme 2 (ACE2) [J].

To, KF ;

Lo, AW .

JOURNAL OF PATHOLOGY, 2004, 203 (03) :740-743

[35] Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review [J].

Aleksova, Aneta ;

Gagno, Giulia ;

Sinagra, Gianfranco ;

Beltrami, Antonio Paolo ;

Janjusevic, Milijana ;

Ippolito, Giuseppe ;

Zumla, Alimuddin ;

Fluca, Alessandra Lucia ;

Ferro, Federico .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (09)

[36] Generation of a SARS-CoV-2-susceptible mouse model using adenovirus vector expressing human angiotensin-converting enzyme 2 driven by an elongation factor 1α promoter with leftward orientation [J].

Matsumoto, Yusuke ;

Honda, Tomoko ;

Yasui, Fumihiko ;

Endo, Akinori ;

Sanada, Takahiro ;

Toyama, Sakiko ;

Takagi, Asako ;

Munakata, Tsubasa ;

Kono, Risa ;

Yamaji, Kenzaburo ;

Yamamoto, Naoki ;

Saeki, Yasushi ;

Kohara, Michinori .

FRONTIERS IN IMMUNOLOGY, 2024, 15

[37] Mechanisms of SARS-CoV-2 Transmission and Pathogenesis [J].

Harrison, Andrew G. ;

Lin, Tao ;

Wang, Penghua .

TRENDS IN IMMUNOLOGY, 2020, 41 (12) :1100-1115

[38] High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme [J].

Esparza, Thomas J. ;

Martin, Negin P. ;

Anderson, George P. ;

Goldman, Ellen R. ;

Brody, David L. .

SCIENTIFIC REPORTS, 2020, 10 (01)

[39] The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data [J].

Malato, Joao ;

Sotzny, Franziska ;

Bauer, Sandra ;

Freitag, Helma ;

Fonseca, Andre ;

Grabowska, Anna D. ;

Graca, Luis ;

Cordeiro, Clara ;

Nacul, Luis ;

Lacerda, Eliana M. ;

Castro-Marrero, Jesus ;

Scheibenbogen, Carmen ;

Westermeier, Francisco ;

Sepulveda, Nuno .

HELIYON, 2021, 7 (08)

[40] Sequence difference of angiotensin-converting enzyme 2 between nonhuman primates affects its binding-affinity with SARS-CoV-2 S receptor binding domain [J].

Zhou, Xiaojun ;

Zhao, Jingjing ;

Qiu, Yefeng ;

Jia, Rui .

BIOSAFETY AND HEALTH, 2022, 4 (05) :293-298

← 1 2 3 4 5 →