This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McCray, P. B.
Right arrow Articles by Perlman, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCray, P. B., Jr.
Right arrow Articles by Perlman, S.

 Previous Article  |  Next Article 

Journal of Virology, January 2007, p. 813-821, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.02012-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus{triangledown}

Paul B. McCray Jr.,1,6* Lecia Pewe,2 Christine Wohlford-Lenane,1 Melissa Hickey,1 Lori Manzel,3 Lei Shi,3 Jason Netland,5 Hong Peng Jia,1 Carmen Halabi,2,6 Curt D. Sigmund,2,6 David K. Meyerholz,4 Patricia Kirby,4 Dwight C. Look,3 and Stanley Perlman1,2,5*

Departments of Pediatrics,1 Microbiology,2 Internal Medicine,3 Pathology,4 Interdisciplinary Programs in Immunology,5 Genetics, University of Iowa, Iowa City, Iowa 522426

Received 24 September 2006/ Accepted 20 October 2006

The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.

* Corresponding author. Mailing address for Paul B. McCray, Jr.: Department of Pediatrics, University of Iowa, Iowa City, IA 52242. Phone: (319) 335-6844. Fax: (319) 335-6925. E-mail: Paul-McCray{at}uiowa.edu. Mailing address for Stanley Perlman: Department of Microbiology, University of Iowa, Iowa City, IA 52242. Phone: (319) 335-8549. Fax: (319) 335-9999. E-mail: stanley-perlman{at}uiowa.edu.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 813-821, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.02012-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yoshikawa, N., Yoshikawa, T., Hill, T., Huang, C., Watts, D. M., Makino, S., Milligan, G., Chan, T., Peters, C. J., Tseng, C.-T. K. (2009). Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. J. Virol. 83: 5451-5465 [Abstract] [Full Text]  
  • Zhao, J., Falcon, A., Zhou, H., Netland, J., Enjuanes, L., Perez Brena, P., Perlman, S. (2009). Severe Acute Respiratory Syndrome Coronavirus Protein 6 Is Required for Optimal Replication. J. Virol. 83: 2368-2373 [Abstract] [Full Text]  
  • Netland, J., Meyerholz, D. K., Moore, S., Cassell, M., Perlman, S. (2008). Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2. J. Virol. 82: 7264-7275 [Abstract] [Full Text]  
  • Li, F. (2008). Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections. J. Virol. 82: 6984-6991 [Abstract] [Full Text]  
  • Hussain, S., Perlman, S., Gallagher, T. M. (2008). Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Hepatitis Virus Infections by More than One Mechanism. J. Virol. 82: 7212-7222 [Abstract] [Full Text]  
  • Narayanan, K., Huang, C., Lokugamage, K., Kamitani, W., Ikegami, T., Tseng, C.-T. K., Makino, S. (2008). Severe Acute Respiratory Syndrome Coronavirus nsp1 Suppresses Host Gene Expression, Including That of Type I Interferon, in Infected Cells. J. Virol. 82: 4471-4479 [Abstract] [Full Text]  
  • Miura, T. A., Travanty, E. A., Oko, L., Bielefeldt-Ohmann, H., Weiss, S. R., Beauchemin, N., Holmes, K. V. (2008). The Spike Glycoprotein of Murine Coronavirus MHV-JHM Mediates Receptor-Independent Infection and Spread in the Central Nervous Systems of Ceacam1a / Mice. J. Virol. 82: 755-763 [Abstract] [Full Text]  
  • Schaecher, S. R., Touchette, E., Schriewer, J., Buller, R. M., Pekosz, A. (2007). Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis. J. Virol. 81: 11054-11068 [Abstract] [Full Text]  
  • Cheng, V. C. C., Lau, S. K. P., Woo, P. C. Y., Yuen, K. Y. (2007). Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection. Clin. Microbiol. Rev. 20: 660-694 [Abstract] [Full Text]  
  • Rockx, B., Sheahan, T., Donaldson, E., Harkema, J., Sims, A., Heise, M., Pickles, R., Cameron, M., Kelvin, D., Baric, R. (2007). Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice. J. Virol. 81: 7410-7423 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»