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User name	Nicolas Tchitchek
Email	nicolas.tchitchek@ihes.fr
Phone / Fax number	0033610887604 /
Location	Institut des Hautes Ã‰tudes Scientifiques (Systems Epigenomics Group) - 35, route de Chartres - 91440 Bures-sur-Yvette, FRANCE

Scientific description

Highly pathogenic respiratory viruses (such as influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS-CoV) infect host animals and cause a multitude of transcriptional changes en route to host lethality. Microarrays have been used to investigate these changes in numerous studies, but data from these studies have not yet been aggregated and mined in a systematic manner. In this study we analyzed a compendium of host transcriptional responses to these and other respiratory viruses and identified signature genes that were oppositely regulated in high- and low-pathogenic infections on a consistent basis. We validated signature genes using various computational methods and characterized them using functional analysis. In addition we tested the predictive capability of these genes on an external data set. These genes point to several mechanisms that may be broadly found in high-pathogenic infections, including the down-regulation of enzymatic and anti-inflammatory pathways, which may help direct future experiments.

Technical description

Please refer to references papers for technical descriptions.

References

Nature. 2006 Oct 5;443(7111):578-81. Epub 2006 Sep 27.
Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus.
Kash JC, Tumpey TM, Proll SC, Carter V, Perwitasari O, Thomas MJ, Basler CF, Palese P, Taubenberger JK, GarcÃa-Sastre A, Swayne DE, Katze MG.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/17006449

Genes Brain Behav. 2008 Mar;7(2):173-83. Epub 2007 Aug 13.
Gene expression in lung and basal forebrain during influenza infection in mice.
Ding M, Lu L, Toth LA.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/17696998

J Virol. 2009 Oct;83(20):10417-26. Epub 2009 Aug 12.
Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice.
Boon AC, deBeauchamp J, Hollmann A, Luke J, Kotb M, Rowe S, Finkelstein D, Neale G, Lu L, Williams RW, Webby RJ.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/19706712

J Virol. 2010 Aug;84(15):7613-24. Epub 2010 May 26.
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.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/20504916

J Virol. 2008 Oct;82(19):9465-76. Epub 2008 Jul 16.
Genomic analysis reveals age-dependent innate immune responses to severe acute respiratory syndrome coronavirus.
Baas T, Roberts A, Teal TH, Vogel L, Chen J, Tumpey TM, Katze MG, Subbarao K.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/18632870

J Virol. 2009 Jul;83(14):7062-74. Epub 2009 May 6.
Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection.
Rockx B, Baas T, Zornetzer GA, Haagmans B, Sheahan T, Frieman M, Dyer MD, Teal TH, Proll S, van den Brand J, Baric R, Katze MG.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/19420084

J Interferon Cytokine Res. 2010 Apr;30(4):263-72.
Double-stranded RNA-activated protein kinase regulates early innate immune responses during respiratory syncytial virus infection.
Minor RA, Limmon GV, Miller-DeGraff L, Dixon D, Andrews DM, Kaufman RJ, Imani F.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/20038207

J Virol. 2009 Nov;83(21):11102-15. Epub 2009 Aug 19.
A single-amino-acid substitution in a polymerase protein of an H5N1 influenza virus is associated with systemic infection and impaired T-cell activation in mice.
Fornek JL, Gillim-Ross L, Santos C, Carter V, Ward JM, Cheng LI, Proll S, Katze MG, Subbarao K.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/19692471

P58(IPK): a novel "CIHD" member of the host innate defense response against pathogenic virus infection.
Goodman AG, Fornek JL, Medigeshi GR, Perrone LA, Peng X, Dyer MD, Proll SC, Knoblaugh SE, Carter VS, Korth MJ, Nelson JA, Tumpey TM, Katze MG.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/19461876

RosenthalUP

J Virol. 2010 Nov;84(21):11297-309. Epub 2010 Aug 11.
Transcriptomic analysis reveals a mechanism for a prefibrotic phenotype in STAT1 knockout mice during severe acute respiratory syndrome coronavirus infection.
Zornetzer GA, Frieman MB, Rosenzweig E, Korth MJ, Page C, Baric RS, Katze MG.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/20702617