This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Baas, T.
Right arrow Articles by Subbarao, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baas, T.
Right arrow Articles by Subbarao, K.

 Previous Article  |  Next Article 

Journal of Virology, October 2008, p. 9465-9476, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00489-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genomic Analysis Reveals Age-Dependent Innate Immune Responses to Severe Acute Respiratory Syndrome Coronavirus{triangledown} ,{dagger}

Tracey Baas,1* Anjeanette Roberts,2 Thomas H. Teal,1 Leatrice Vogel,2 Jun Chen,2 Terrence M. Tumpey,3 Michael G. Katze,1 and Kanta Subbarao2

Department of Microbiology, University of Washington, Seattle, Washington,1 Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland,2 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia3

Received 5 March 2008/ Accepted 3 July 2008

The relationship between immunosenescence and the host response to virus infection is poorly understood at the molecular level. Two different patterns of pulmonary host responses to virus were observed when gene expression profiles from severe acute respiratory syndrome coronavirus (SARS-CoV)-infected young mice that show minimal disease were compared to those from SARS-CoV-infected aged mice that develop pneumonitis. In young mice, genes related to cellular development, cell growth, and cell cycle were downregulated during peak viral replication, and these transcripts returned to basal levels as virus was cleared. In contrast, aged mice had a greater number of upregulated immune response and cell-to-cell signaling genes, and the expression of many genes was sustained even after viral clearance, suggesting an exacerbated host response to virus. Interestingly, in SARS-CoV-infected aged mice, a subset of genes, including Tnfa, Il6, Ccl2, Ccl3, Cxcl10, and Ifng, was induced in a biphasic pattern that correlated with peak viral replication and a subsequent influx of lymphocytes and severe histopathologic changes in the lungs. We provide insight into gene expression profiles and molecular signatures underlying immunosenescence in the context of the host response to viral infection.

* Corresponding author. Mailing address: Department of Microbiology, Box 358070, University of Washington, Seattle, WA 98195-8070. Phone: (206) 732-6119. Fax: (206) 732-6056. E-mail: traceybaas{at}gmail.com

{triangledown} Published ahead of print on 16 July 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, October 2008, p. 9465-9476, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00489-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wohlford-Lenane, C. L., Meyerholz, D. K., Perlman, S., Zhou, H., Tran, D., Selsted, M. E., McCray, P. B. Jr. (2009). Rhesus Theta-Defensin Prevents Death in a Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Pulmonary Disease. J. Virol. 83: 11385-11390 [Abstract] [Full Text]  
  • Rockx, B., Baas, T., Zornetzer, G. A., Haagmans, B., Sheahan, T., Frieman, M., Dyer, M. D., Teal, T. H., Proll, S., van den Brand, J., Baric, R., Katze, M. G. (2009). Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection. J. Virol. 83: 7062-7074 [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»