Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.

The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Cristian Cillóniz, Kyoko Shinya, Xinxia Peng, Marcus J Korth, Sean C Proll, Lauri D Aicher, Victoria S Carter, Jean H Chang, Darwyn Kobasa, Friedericke Feldmann, James E Strong, Heinz Feldmann, Yoshihiro Kawaoka, Michael G Katze
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2009
Materias:
Acceso en línea:https://doaj.org/article/69146b6be9d7436f83aa9050f9bb54c6
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:69146b6be9d7436f83aa9050f9bb54c6
record_format dspace
spelling oai:doaj.org-article:69146b6be9d7436f83aa9050f9bb54c62021-11-25T05:47:36ZLethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.1553-73661553-737410.1371/journal.ppat.1000604https://doaj.org/article/69146b6be9d7436f83aa9050f9bb54c62009-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19798428/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.Cristian CillónizKyoko ShinyaXinxia PengMarcus J KorthSean C ProllLauri D AicherVictoria S CarterJean H ChangDarwyn KobasaFriedericke FeldmannJames E StrongHeinz FeldmannYoshihiro KawaokaMichael G KatzePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 10, p e1000604 (2009)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Cristian Cillóniz
Kyoko Shinya
Xinxia Peng
Marcus J Korth
Sean C Proll
Lauri D Aicher
Victoria S Carter
Jean H Chang
Darwyn Kobasa
Friedericke Feldmann
James E Strong
Heinz Feldmann
Yoshihiro Kawaoka
Michael G Katze
Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.
description The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.
format article
author Cristian Cillóniz
Kyoko Shinya
Xinxia Peng
Marcus J Korth
Sean C Proll
Lauri D Aicher
Victoria S Carter
Jean H Chang
Darwyn Kobasa
Friedericke Feldmann
James E Strong
Heinz Feldmann
Yoshihiro Kawaoka
Michael G Katze
author_facet Cristian Cillóniz
Kyoko Shinya
Xinxia Peng
Marcus J Korth
Sean C Proll
Lauri D Aicher
Victoria S Carter
Jean H Chang
Darwyn Kobasa
Friedericke Feldmann
James E Strong
Heinz Feldmann
Yoshihiro Kawaoka
Michael G Katze
author_sort Cristian Cillóniz
title Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.
title_short Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.
title_full Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.
title_fullStr Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.
title_full_unstemmed Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.
title_sort lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/69146b6be9d7436f83aa9050f9bb54c6
work_keys_str_mv AT cristiancilloniz lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT kyokoshinya lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT xinxiapeng lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT marcusjkorth lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT seancproll lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT lauridaicher lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT victoriascarter lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT jeanhchang lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT darwynkobasa lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT friederickefeldmann lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT jamesestrong lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT heinzfeldmann lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT yoshihirokawaoka lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
AT michaelgkatze lethalinfluenzavirusinfectioninmacaquesisassociatedwithearlydysregulationofinflammatoryrelatedgenes
_version_ 1718414460375269376