tetano
Editor, Senior Moderator
J Virol. 2010 May 26. [Epub ahead of print]
Lethal dissemination of H5N1 influenza virus is associated with dysregulation of inflammation and lipoxin signaling in a mouse model of infection.
Cilloniz C, Pantin-Jackwood MJ, Ni C, Goodman AG, Peng X, Proll SC, Carter VS, Rosenzweig ER, Szretter KJ, Katz JM, Korth MJ, Swayne DE, Tumpey TM, Katze MG.
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195; Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 30606; Department of Medicine, Washington University, Saint Louis, MO 63110; Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333; Washington National Primate Research Center, University of Washington, Seattle, Washington 98195.
Abstract
Periodic outbreaks of highly pathogenic avian H5N1 influenza viruses, and the current H1N1 pandemic, highlight the need for a more detailed understanding of influenza virus pathogenesis. To investigate the host transcriptional response induced by pathogenic influenza viruses, we used a functional genomics approach to compare gene expression profiles in lungs from 129S6/SvEv mice infected with either the fully reconstructed H1N1 1918 pandemic virus (1918) or the highly pathogenic avian H5N1 virus Vietnam/1203/04 (VN/1203). Although both viruses reached similar titers in the lung and caused a lethal infection, the mean time of death was 6 days for VN/1203-infected animals and 9 days for mice infected with the 1918 virus. VN/1203-infected animals also exhibited an earlier and more potent inflammatory response. This response included induction of genes encoding components of the inflammasome. VN/1203 was also able to disseminate to multiple organs, including the brain, which correlated with changes in the expression of genes associated with hematological functions and lipoxin biogenesis and signaling. Both viruses elicited expression of type I interferon (IFN)-regulated genes in wild-type mice and to a lesser extent in mice lacking the type I IFN receptor, suggesting alternative or redundant pathways for IFN signaling. Our findings suggest that VN/1203 is more pathogenic in mice as a consequence of several factors, including the early and sustained induction of the inflammatory response, the additive or synergistic effects of up-regulated components of the immune response, and inhibition of lipoxin-mediated anti-inflammatory responses, which correlated with the ability of VN/1203 to disseminate to extrapulmonary organs.
PMID: 20504916 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20504916
Lethal dissemination of H5N1 influenza virus is associated with dysregulation of inflammation and lipoxin signaling in a mouse model of infection.
Cilloniz C, Pantin-Jackwood MJ, Ni C, Goodman AG, Peng X, Proll SC, Carter VS, Rosenzweig ER, Szretter KJ, Katz JM, Korth MJ, Swayne DE, Tumpey TM, Katze MG.
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195; Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 30606; Department of Medicine, Washington University, Saint Louis, MO 63110; Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333; Washington National Primate Research Center, University of Washington, Seattle, Washington 98195.
Abstract
Periodic outbreaks of highly pathogenic avian H5N1 influenza viruses, and the current H1N1 pandemic, highlight the need for a more detailed understanding of influenza virus pathogenesis. To investigate the host transcriptional response induced by pathogenic influenza viruses, we used a functional genomics approach to compare gene expression profiles in lungs from 129S6/SvEv mice infected with either the fully reconstructed H1N1 1918 pandemic virus (1918) or the highly pathogenic avian H5N1 virus Vietnam/1203/04 (VN/1203). Although both viruses reached similar titers in the lung and caused a lethal infection, the mean time of death was 6 days for VN/1203-infected animals and 9 days for mice infected with the 1918 virus. VN/1203-infected animals also exhibited an earlier and more potent inflammatory response. This response included induction of genes encoding components of the inflammasome. VN/1203 was also able to disseminate to multiple organs, including the brain, which correlated with changes in the expression of genes associated with hematological functions and lipoxin biogenesis and signaling. Both viruses elicited expression of type I interferon (IFN)-regulated genes in wild-type mice and to a lesser extent in mice lacking the type I IFN receptor, suggesting alternative or redundant pathways for IFN signaling. Our findings suggest that VN/1203 is more pathogenic in mice as a consequence of several factors, including the early and sustained induction of the inflammatory response, the additive or synergistic effects of up-regulated components of the immune response, and inhibition of lipoxin-mediated anti-inflammatory responses, which correlated with the ability of VN/1203 to disseminate to extrapulmonary organs.
PMID: 20504916 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20504916