Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment
Copyright © 2020 Elsevier Inc. All rights reserved..
COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:182 |
|---|---|
| Enthalten in: |
Cell - 182(2020), 3 vom: 06. Aug., Seite 734-743.e5 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sun, Jing [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 28.08.2020 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.cell.2020.06.010 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM312208839 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM312208839 | ||
| 003 | DE-627 | ||
| 005 | 20240328235646.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.cell.2020.06.010 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1353.xml |
| 035 | |a (DE-627)NLM312208839 | ||
| 035 | |a (NLM)32643603 | ||
| 035 | |a (PII)S0092-8674(20)30741-8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sun, Jing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 28.08.2020 | ||
| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a mouse model | |
| 650 | 4 | |a pathogenesis | |
| 650 | 4 | |a therapeutics | |
| 650 | 4 | |a vaccine | |
| 650 | 7 | |a IFNG protein, mouse |2 NLM | |
| 650 | 7 | |a Ifnar1 protein, mouse |2 NLM | |
| 650 | 7 | |a STAT1 Transcription Factor |2 NLM | |
| 650 | 7 | |a Stat1 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptor, Interferon alpha-beta |2 NLM | |
| 650 | 7 | |a 156986-95-7 |2 NLM | |
| 650 | 7 | |a Interferon-gamma |2 NLM | |
| 650 | 7 | |a 82115-62-6 |2 NLM | |
| 650 | 7 | |a Peptidyl-Dipeptidase A |2 NLM | |
| 650 | 7 | |a EC 3.4.15.1 |2 NLM | |
| 650 | 7 | |a ACE2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Ace2 protein, mouse |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Zhuang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Roy Lok-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Donglan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jicheng |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jiangping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Airu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jingxian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaobo |e verfasserin |4 aut | |
| 700 | 1 | |a Xi, Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Rongchang |e verfasserin |4 aut | |
| 700 | 1 | |a Alshukairi, Abeer N |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhaoyong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chunke |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiaofang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Xiaomin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Dingbin |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Liyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuo, Jianfen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yanqun |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Shuxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Yongxia |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Kui |e verfasserin |4 aut | |
| 700 | 1 | |a Leidinger, Mariah R |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiekai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yimin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Nanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Meyerholz, David K |e verfasserin |4 aut | |
| 700 | 1 | |a McCray, Paul B |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Perlman, Stanley |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell |d 1974 |g 182(2020), 3 vom: 06. Aug., Seite 734-743.e5 |w (DE-627)NLM000088935 |x 1097-4172 |7 nnns |
| 773 | 1 | 8 | |g volume:182 |g year:2020 |g number:3 |g day:06 |g month:08 |g pages:734-743.e5 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.cell.2020.06.010 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 182 |j 2020 |e 3 |b 06 |c 08 |h 734-743.e5 | ||