SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

被引：1045

作者：

Hou, Yixuan J. ^{[1
]}

Okuda, Kenichi ^{[3
]}

Edwards, Caitlin E. ^{[1
]}

Martinez, David R. ^{[1
]}

Asakura, Takanori ^{[3
]}

Dinnon, Kenneth H., III ^{[2
]}

Kato, Takafumi ^{[3
]}

Lee, Rhianna E. ^{[3
]}

Yount, Boyd L. ^{[1
]}

Mascenik, Teresa M. ^{[3
]}

Chen, Gang ^{[3
]}

Olivier, Kenneth N. ^{[16
]}

Ghio, Andrew ^{[17
]}

Tse, Longping, V ^{[1
]}

Leist, Sarah R. ^{[1
]}

Gralinski, Lisa E. ^{[1
]}

Schafer, Alexandra ^{[1
]}

Dang, Hong ^{[3
]}

Gilmore, Rodney ^{[3
]}

Nakano, Satoko ^{[3
]}

Sun, Ling ^{[3
]}

Fulcher, M. Leslie ^{[3
]}

Livraghi-Butrico, Alessandra ^{[3
]}

Nicely, Nathan, I ^{[4
]}

Cameron, Mark ^{[11
]}

Cameron, Cheryl ^{[12
]}

Kelvin, David J. ^{[10
,18
]}

de Silva, Aravinda ^{[2
]}

Margolis, David M. ^{[2
,5
,6
]}

Markmann, Alena ^{[5
]}

Bartelt, Luther ^{[5
]}

Zumwalt, Ross ^{[13
]}

Martinez, Fernando J. ^{[14
]}

Salvatore, Steven P. ^{[15
]}

Borczuk, Alain ^{[15
]}

Tata, Purushothama R. ^{[9
]}

Sontake, Vishwaraj ^{[9
]}

Kimple, Adam ^{[7
]}

Jaspers, Ilona ^{[8
]}

O'Neal, Wanda K. ^{[3
]}

Randell, Scott H. ^{[3
]}

Boucher, Richard C. ^{[3
]}

Baric, Ralph S. ^{[1
,2
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA

[3] Univ N Carolina, Marsico Lung Inst, Chapel Hill, NC 27515 USA

[4] Univ N Carolina, Prot Express & Purificat Core, Chapel Hill, NC 27515 USA

[5] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA

[6] Univ N Carolina, HIV Cure Ctr, Chapel Hill, NC 27515 USA

[7] Univ N Carolina, Dept Otolaryngol, Chapel Hill, NC 27515 USA

[8] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27515 USA

[9] Duke Univ, Med Ctr, Dept Cell Biol, Regenerat Next Initiat, Durham, NC 27710 USA

[10] Dalhousie Univ, Canadian Ctr Vaccinol, Dept Microbiol & Immunol, Halifax, NS, Canada

[11] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[12] Case Western Reserve Univ, Dept Nutr, Cleveland, OH 44106 USA

[13] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA

[14] Cornell Univ, Joan & Sanford I Weill Med Coll, Div Pulm & Crit Care Med, New York, NY 10021 USA

[15] Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Pathol, New York, NY 10021 USA

[16] NHLBI, Lab Chron Airway Infect, Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA

[17] US EPA, Natl Hlth & Environm Effects Res Lab, Chapel Hill, NC USA

[18] Shantou Univ, Lab Immunol, Med Coll, Shantou, Guangdong, Peoples R China

来源：

CELL | 2020年 / 182卷 / 02期

关键词：

CORONAVIRUS SPIKE PROTEIN; ENZYME; 2; ACE2; SARS CORONAVIRUS; CELL ENTRY; CDNA-CLONE; MERS-COV; VIRUS; NEUTRALIZATION; ACTIVATION; ASPIRATION;

D O I：

10.1016/j.cell.2020.05.042

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：

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.

引用

页码：429 / +

页数：32

共 50 条

[31] Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection
Sala, Simone
Peretto, Giovanni
Gramegna, Mario
Palmisano, Anna
Villatore, Andrea
Vignale, Davide
De Cobelli, Francesco
Tresoldi, Moreno
Cappelletti, Alberto Maria
Basso, Cristina
Godino, Cosmo
Esposito, Antonio
EUROPEAN HEART JOURNAL, 2020, 41 (19) : 1861 - 1862
[32] A mouse model of lethal respiratory dysfunction for SARS-CoV-2 infection
Gan, Esther S.
Syenina, Ayesa
Linster, Martin
Ng, Benson
Zhang, Summer L.
Watanabe, Satoru
Rajarethinam, Ravisankar
Tan, Hwee Cheng
Smith, Gavin J. D.
Ooi, Eng Eong
ANTIVIRAL RESEARCH, 2021, 193
[33] Acute Myopericarditis in a Patient With Mild SARS-CoV-2 Respiratory Infection
Labani, Aissam
Germain, Philippe
Douchet, Marie-Pierre
Beghi, Mustapha
Von Hunolstein, Jean Jacques
Zeyons, Floriane
Roy, Catherine
El Ghannudi, Soraya
CJC OPEN, 2020, 2 (05) : 435 - 437
[34] Detection of respiratory viruses in patients with suspected SARS-CoV-2 infection
Reina, Jordi
Suarez, Loreto
Lara, Paula
ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA, 2021, 39 (01): : 52 - 53
[35] Respiratory function in asthmatic patients after SARS-coV-2 infection
Lobato, M.
Goncalves, T.
Romeira, A. M.
Pita, J.
Brito, A.
Santos, S.
Moura, S.
Brito, M. J.
Leiria, Pinto P.
ALLERGY, 2021, 76 : 207 - 207
[36] BEYOND RESPIRATORY DAMAGE - NEUROLOGICAL INVOLVEMENT IN SARS-CoV-2 INFECTION
Diaconu, Iulia Elena
Onofrei, Maria Ioana
Mihai, Ioana Florina
Leonte, Georgiana Enache
Hurmuzache, M.
Luca, Mihaela Catalina
MEDICAL-SURGICAL JOURNAL-REVISTA MEDICO-CHIRURGICALA, 2022, 126 (04): : 504 - 510
[37] Use of anakinra in the treatment of SARS-CoV-2 severe respiratory infection
Figuero-Perez, Luis
Olivares-Hernandez, Alejandro
Escala-Cornejo, Roberto A.
Cruz-Hernandez, Juan J.
REUMATOLOGIA CLINICA, 2023, 19 (02): : 121 - 121
[38] On the Sensitivity and Specificity of Postmortem Upper Respiratory Tract Testing for SARS-CoV-2
Hall, Jennifer A.
Harris, Ross J.
Emmett, Hannah E.
Lowe, Belinda
Singanayagam, Anika
Twohig, Katherine A.
Zaidi, Asad
Kall, Meaghan
Zambon, Maria
Dabrera, Gavin
JOURNAL OF INFECTIOUS DISEASES, 2021, 224 (03): : 389 - 394
[39] Uncover a microbiota signature of upper respiratory tract in patients with SARS-CoV-2 +
Massimo Bellato
Marco Cappellato
Francesca Longhin
Claudia Del Vecchio
Giuseppina Brancaccio
Anna Maria Cattelan
Paola Brun
Claudio Salaris
Ignazio Castagliuolo
Barbara Di Camillo
Scientific Reports, 13
[40] Rapid diagnosis of SARS-CoV-2 pneumonia on lower respiratory tract specimens
Vanessa De Pace
Patrizia Caligiuri
Valentina Ricucci
Nicola Nigro
Barbara Galano
Valeria Visconti
Giorgio Da Rin
Bianca Bruzzone
BMC Infectious Diseases, 21

← 1 2 3 4 5 →