Giuseppe
Emeritus
J Virol. 2009 Aug 12. [Epub ahead of print]
The NS1 Protein of the 1918 Pandemic Influenza Virus Blocks Host Interferon and Lipid Metabolism Pathways.
Billharz R, Zeng H, Proll SC, Korth MJ, Lederer S, Albrecht R, Goodman AG, Rosenzweig E, Tumpey TM, Garc?a-Sastre A, Katze MG. - Department of Microbiology and Washington National Primate Research Center, University of Washington, Seattle, Washington; Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and Department of Microbiology, Department of Medicine, Division of Infectious Diseases, and Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York.
The 'Spanish Influenza' of 1918 claimed an unprecedented number of lives, yet the determinants of virulence for this virus are still not fully understood. Here, we used functional genomics and an in vitro human lung epithelial cell infection model to define the global host transcriptional response to the 8-gene 1918 virus. To better understand the role of the 1918 virus NS1 gene, we also evaluated the host response to a reassortant 1918 virus containing the NS1 gene from A/Texas/36/91 (a seasonal isolate of human influenza), as well as the host response to a reassortant of A/Texas/36/91 containing the 1918 NS1 gene. Genomic analyses revealed that the 1918 virus blocked the transcription of multiple interferon-stimulated genes and also down-regulated a network of genes associated with lipid metabolism. In contrast, the expression of genes encoding chemokines and cytokines, which serve to attract infiltrating immune cells, was up-regulated. Viruses containing the NS1 gene from A/Texas/36/91 induced a significant increase in type-I interferon signaling, but did not repress lipid metabolism. The 1918 NS1 gene may therefore have contributed to the virulence of the 1918 pandemic virus by disrupting the innate immune response, inducing hypercytokinemia, and by blocking the transcription of certain lipid-based pro-inflammatory mediators that function as part of the host antiviral response.
PMID: 19706713 [PubMed - as supplied by publisher]
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The NS1 Protein of the 1918 Pandemic Influenza Virus Blocks Host Interferon and Lipid Metabolism Pathways.
Billharz R, Zeng H, Proll SC, Korth MJ, Lederer S, Albrecht R, Goodman AG, Rosenzweig E, Tumpey TM, Garc?a-Sastre A, Katze MG. - Department of Microbiology and Washington National Primate Research Center, University of Washington, Seattle, Washington; Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and Department of Microbiology, Department of Medicine, Division of Infectious Diseases, and Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York.
The 'Spanish Influenza' of 1918 claimed an unprecedented number of lives, yet the determinants of virulence for this virus are still not fully understood. Here, we used functional genomics and an in vitro human lung epithelial cell infection model to define the global host transcriptional response to the 8-gene 1918 virus. To better understand the role of the 1918 virus NS1 gene, we also evaluated the host response to a reassortant 1918 virus containing the NS1 gene from A/Texas/36/91 (a seasonal isolate of human influenza), as well as the host response to a reassortant of A/Texas/36/91 containing the 1918 NS1 gene. Genomic analyses revealed that the 1918 virus blocked the transcription of multiple interferon-stimulated genes and also down-regulated a network of genes associated with lipid metabolism. In contrast, the expression of genes encoding chemokines and cytokines, which serve to attract infiltrating immune cells, was up-regulated. Viruses containing the NS1 gene from A/Texas/36/91 induced a significant increase in type-I interferon signaling, but did not repress lipid metabolism. The 1918 NS1 gene may therefore have contributed to the virulence of the 1918 pandemic virus by disrupting the innate immune response, inducing hypercytokinemia, and by blocking the transcription of certain lipid-based pro-inflammatory mediators that function as part of the host antiviral response.
PMID: 19706713 [PubMed - as supplied by publisher]
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