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 Kash, J. C.
Right arrow Articles by Tumpey, T. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kash, J. C.
Right arrow Articles by Tumpey, T. M.

 Previous Article  |  Next Article 

Journal of Virology, September 2004, p. 9499-9511, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9499-9511.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus

John C. Kash,1* Christopher F. Basler,2 Adolfo García-Sastre,2 Victoria Carter,1 Rosalind Billharz,1 David E. Swayne,3 Ronald M. Przygodzki,4 Jeffery K. Taubenberger,4 Michael G. Katze,1,5 and Terrence M. Tumpey3,{dagger}

Department of Microbiology, School of Medicine,1 Washington National Primate Research Center, University of Washington, Seattle, Washington,5 Department of Microbiology, Mount Sinai School of Medicine, New York, New York,2 Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia,3 Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Washington, D.C.4

Received 10 November 2003/ Accepted 2 April 2004

To understand more fully the molecular events associated with highly virulent or attenuated influenza virus infections, we have studied the effects of expression of the 1918 hemagglutinin (HA) and neuraminidase (NA) genes during viral infection in mice under biosafety level 3 (agricultural) conditions. Using histopathology and cDNA microarrays, we examined the consequences of expression of the HA and NA genes of the 1918 pandemic virus in a recombinant influenza A/WSN/33 virus compared to parental A/WSN/33 virus and to an attenuated virus expressing the HA and NA genes from A/New Caledonia/20/99. The 1918 HA/NA:WSN and WSN recombinant viruses were highly lethal for mice and displayed severe lung pathology in comparison to the nonlethal New Caledonia HA/NA:WSN recombinant virus. Expression microarray analysis performed on lung tissues isolated from the infected animals showed activation of many genes involved in the inflammatory response, including cytokine, apoptosis, and lymphocyte genes that were common to all three infection groups. However, consistent with the histopathology studies, the WSN and 1918 HA/NA:WSN recombinant viruses showed increased up-regulation of genes associated with activated T cells and macrophages, as well as genes involved in apoptosis, tissue injury, and oxidative damage that were not observed in the New Caledonia HA/NA:WSN recombinant virus-infected mice. These studies document clear differences in gene expression profiles that were correlated with pulmonary disease pathology induced by virulent and attenuated influenza virus infections.

* Corresponding author. Mailing address: Department of Microbiology, University of Washington School of Medicine, Box 358070, Seattle, WA 98195-8070. Phone: (206) 732-6158. Fax: (206) 732-6055. E-mail: jkash{at}u.washington.edu.

{dagger} Present address: Influenza Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.

Journal of Virology, September 2004, p. 9499-9511, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9499-9511.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Billharz, R., Zeng, H., Proll, S. C., Korth, M. J., Lederer, S., Albrecht, R., Goodman, A. G., Rosenzweig, E., Tumpey, T. M., Garcia-Sastre, A., Katze, M. G. (2009). The NS1 Protein of the 1918 Pandemic Influenza Virus Blocks Host Interferon and Lipid Metabolism Pathways. J. Virol. 83: 10557-10570 [Abstract] [Full Text]  
  • Schmolke, M., Viemann, D., Roth, J., Ludwig, S. (2009). Essential Impact of NF-{kappa}B Signaling on the H5N1 Influenza A Virus-Induced Transcriptome. J. Immunol. 183: 5180-5189 [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]  
  • Teijaro, J. R., Njau, M. N., Verhoeven, D., Chandran, S., Nadler, S. G., Hasday, J., Farber, D. L. (2009). Costimulation Modulation Uncouples Protection from Immunopathology in Memory T Cell Responses to Influenza Virus. J. Immunol. 182: 6834-6843 [Abstract] [Full Text]  
  • Qi, L., Kash, J. C., Dugan, V. G., Wang, R., Jin, G., Cunningham, R. E., Taubenberger, J. K. (2009). Role of Sialic Acid Binding Specificity of the 1918 Influenza Virus Hemagglutinin Protein in Virulence and Pathogenesis for Mice. J. Virol. 83: 3754-3761 [Abstract] [Full Text]  
  • Al-Garawi, A. A., Fattouh, R., Walker, T. D., Jamula, E. B., Botelho, F., Goncharova, S., Reed, J., Stampfli, M. R., O'Byrne, P. M., Coyle, A. J., Jordana, M. (2009). Acute, but Not Resolved, Influenza A Infection Enhances Susceptibility to House Dust Mite-Induced Allergic Disease. J. Immunol. 182: 3095-3104 [Abstract] [Full Text]  
  • Baas, T., Roberts, A., Teal, T. H., Vogel, L., Chen, J., Tumpey, T. M., Katze, M. G., Subbarao, K. (2008). Genomic Analysis Reveals Age-Dependent Innate Immune Responses to Severe Acute Respiratory Syndrome Coronavirus. J. Virol. 82: 9465-9476 [Abstract] [Full Text]  
  • Xing, Z., Cardona, C. J., Li, J., Dao, N., Tran, T., Andrada, J. (2008). Modulation of the immune responses in chickens by low-pathogenicity avian influenza virus H9N2. J. Gen. Virol. 89: 1288-1299 [Abstract] [Full Text]  
  • Salomon, R., Hoffmann, E., Webster, R. G. (2007). Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc. Natl. Acad. Sci. USA 104: 12479-12481 [Abstract] [Full Text]  
  • Rodriguez, N., Mages, J., Dietrich, H., Wantia, N., Wagner, H., Lang, R., Miethke, T. (2007). MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae. Physiol. Genomics 30: 134-145 [Abstract] [Full Text]  
  • Carter, M. J. (2007). A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. J Med Microbiol 56: 875-883 [Abstract] [Full Text]  
  • Janssen, R., Pennings, J., Hodemaekers, H., Buisman, A., van Oosten, M., de Rond, L., Ozturk, K., Dormans, J., Kimman, T., Hoebee, B. (2007). Host Transcription Profiles upon Primary Respiratory Syncytial Virus Infection. J. Virol. 81: 5958-5967 [Abstract] [Full Text]  
  • Mibayashi, M., Martinez-Sobrido, L., Loo, Y.-M., Cardenas, W. B., Gale, M. Jr., Garcia-Sastre, A. (2007). Inhibition of Retinoic Acid-Inducible Gene I-Mediated Induction of Beta Interferon by the NS1 Protein of Influenza A Virus. J. Virol. 81: 514-524 [Abstract] [Full Text]  
  • Baas, T., Baskin, C. R., Diamond, D. L., Garcia-Sastre, A., Bielefeldt-Ohmann, H., Tumpey, T. M., Thomas, M. J., Carter, V. S., Teal, T. H., Van Hoeven, N., Proll, S., Jacobs, J. M., Caldwell, Z. R., Gritsenko, M. A., Hukkanen, R. R., Camp, D. G. II, Smith, R. D., Katze, M. G. (2006). Integrated Molecular Signature of Disease: Analysis of Influenza Virus-Infected Macaques through Functional Genomics and Proteomics. J. Virol. 80: 10813-10828 [Abstract] [Full Text]  
  • Pasieka, T. J., Baas, T., Carter, V. S., Proll, S. C., Katze, M. G., Leib, D. A. (2006). Functional genomic analysis of herpes simplex virus type 1 counteraction of the host innate response.. J. Virol. 80: 7600-7612 [Abstract] [Full Text]  
  • Kawada, J.-i., Kimura, H., Kamachi, Y., Nishikawa, K., Taniguchi, M., Nagaoka, K., Kurahashi, H., Kojima, S., Morishima, T. (2006). Analysis of gene-expression profiles by oligonucleotide microarray in children with influenza. J. Gen. Virol. 87: 1677-1683 [Abstract] [Full Text]  
  • Tumpey, T. M., Garcia-Sastre, A., Taubenberger, J. K., Palese, P., Swayne, D. E., Pantin-Jackwood, M. J., Schultz-Cherry, S., Solorzano, A., Van Rooijen, N., Katz, J. M., Basler, C. F. (2005). Pathogenicity of Influenza Viruses with Genes from the 1918 Pandemic Virus: Functional Roles of Alveolar Macrophages and Neutrophils in Limiting Virus Replication and Mortality in Mice. J. Virol. 79: 14933-14944 [Abstract] [Full Text]  
  • Baskin, C. R., Garcia-Sastre, A., Tumpey, T. M., Bielefeldt-Ohmann, H., Carter, V. S., Nistal-Villan, E., Katze, M. G. (2004). Integration of Clinical Data, Pathology, and cDNA Microarrays in Influenza Virus-Infected Pigtailed Macaques (Macaca nemestrina). J. Virol. 78: 10420-10432 [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»