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 De Albuquerque, N.
Right arrow Articles by Levy, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by De Albuquerque, N.
Right arrow Articles by Levy, G. A.

 Previous Article  |  Next Article 

Journal of Virology, November 2006, p. 10382-10394, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00747-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Murine Hepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A/J Mice

Nadine De Albuquerque,1,4 Ehtesham Baig,5 Xuezhong Ma,1,4 Jianhua Zhang,1,4 William He,1,4 Andrea Rowe,1,4 Marlena Habal,1,4 Mingfeng Liu,1,4 Itay Shalev,1,4 Gregory P. Downey,1,4 Reginald Gorczynski,2,4 Jagdish Butany,3 Julian Leibowitz,7 Susan R. Weiss,6 Ian D. McGilvray,2,4,5 M. James Phillips,3,4 Eleanor N. Fish,5 and Gary A. Levy1,4,5*

Departments of Medicine,1 Surgery,2 Pathology,3 the Multi Organ Transplant Program,4 University Health Network, University of Toronto, Toronto, Ontario, Canada,5 Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania,6 Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College Station, Texas7

Received 12 April 2006/ Accepted 5 August 2006

Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack of a readily available animal model. Intranasal infection of A/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MHV-1-infected A/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals. In contrast, other mouse strains developed only mild transitory disease. Infected A/J mice had significantly higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP-1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore, FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly increased in the lungs of infected A/J mice. These animals developed a less robust type I interferon response to MHV-1 infection than resistant C57BL/6J mice, and treatment with recombinant beta interferon improved survival. This study describes a potentially useful small animal model of human SARS, defines its pathogenesis, and suggests treatment strategies.

* Corresponding author. Mailing address: Toronto General Hospital, 585 University Ave., NCSB-11-1236, Toronto, Ontario M5G 2N2, Canada. Phone: (416) 340-5166. Fax: (416) 340-3378. E-mail: glfgl2{at}attglobal.net.

Journal of Virology, November 2006, p. 10382-10394, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00747-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Funk, C. J., Manzer, R., Miura, T. A., Groshong, S. D., Ito, Y., Travanty, E. A., Leete, J., Holmes, K. V., Mason, R. J. (2009). Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response. J. Gen. Virol. 90: 2956-2964 [Abstract] [Full Text]  
  • Miura, T. A., Holmes, K. V. (2009). Host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells. J. Leukoc. Biol. 86: 1145-1151 [Abstract] [Full Text]  
  • Khanolkar, A., Hartwig, S. M., Haag, B. A., Meyerholz, D. K., Epping, L. L., Haring, J. S., Varga, S. M., Harty, J. T. (2009). Protective and Pathologic Roles of the Immune Response to Mouse Hepatitis Virus Type 1: Implications for Severe Acute Respiratory Syndrome. J. Virol. 83: 9258-9272 [Abstract] [Full Text]  
  • Khanolkar, A., Hartwig, S. M., Haag, B. A., Meyerholz, D. K., Harty, J. T., Varga, S. M. (2009). Toll-Like Receptor 4 Deficiency Increases Disease and Mortality after Mouse Hepatitis Virus Type 1 Infection of Susceptible C3H Mice. J. Virol. 83: 8946-8956 [Abstract] [Full Text]  
  • Roth-Cross, J. K., Stokes, H., Chang, G., Chua, M. M., Thiel, V., Weiss, S. R., Gorbalenya, A. E., Siddell, S. G. (2009). Organ-Specific Attenuation of Murine Hepatitis Virus Strain A59 by Replacement of Catalytic Residues in the Putative Viral Cyclic Phosphodiesterase ns2. J. Virol. 83: 3743-3753 [Abstract] [Full Text]  
  • Han, M., Yan, W., Huang, Y., Yao, H., Wang, Z., Xi, D., Li, W., Zhou, Y., Hou, J., Luo, X., Ning, Q. (2008). The Nucleocapsid Protein of SARS-CoV Induces Transcription of hfgl2 Prothrombinase Gene Dependent on C/EBP Alpha. J Biochem 144: 51-62 [Abstract] [Full Text]  
  • Kang, H., Bhardwaj, K., Li, Y., Palaninathan, S., Sacchettini, J., Guarino, L., Leibowitz, J. L., Kao, C. C. (2007). Biochemical and Genetic Analyses of Murine Hepatitis Virus Nsp15 Endoribonuclease. J. Virol. 81: 13587-13597 [Abstract] [Full Text]  
  • Roth-Cross, J. K., Martinez-Sobrido, L., Scott, E. P., Garcia-Sastre, A., Weiss, S. R. (2007). Inhibition of the Alpha/Beta Interferon Response by Mouse Hepatitis Virus at Multiple Levels. J. Virol. 81: 7189-7199 [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»