title: Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems.
abstract: BACKGROUND
  Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades.
  
  
  RESULTS
  In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well-studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms.
  
  
  CONCLUSIONS
  This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models.
authors.affiliation: Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.forename: Harish
authors.initials: H
authors.lastname: Shankaran
authors.forename: Amie J
authors.initials: AJ
authors.lastname: Eisfeld
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Belisle
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neuman
authors.forename: Chengjun
authors.initials: C
authors.lastname: Li
authors.forename: Shannon
authors.initials: S
authors.lastname: McWeeney
authors.forename: Carol
authors.initials: C
authors.lastname: Sabourin
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Waters
mesh_terms: D000818:Animals; D060467:Disease Resistance / Q000235:genetics; D053263:Gene Regulatory Networks; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity; D007251:Influenza, Human / Q000235:genetics* / Q000276:immunology; D008251:Macaca; D051379:Mice; D018448:Models, Immunological; D015999:Multivariate Analysis; D049490:Systems Biology
references.citation: Trends Immunol. 2011 Jan;32(1):34-41
references.pmid: 21147034
references.citation: Virol J. 2010 Sep 09;7:219
references.pmid: 20828378
references.citation: Lancet. 2008 Apr 26;371(9622):1427-34
references.pmid: 18400288
references.citation: Acta Virol. 2006;50(3):151-62
references.pmid: 17131933
references.citation: Biochemistry. 1998 Jun 2;37(22):7941-51
references.pmid: 9609687
references.citation: PLoS Genet. 2005 Sep;1(3):e39
references.pmid: 16470937
references.citation: Lancet. 2004 Feb 21;363(9409):617-9
references.pmid: 14987888
references.citation: Mol Cell Biol. 1987 Nov;7(11):3880-7
references.pmid: 2828918
references.citation: DNA Cell Biol. 2004 Apr;23(4):193-205
references.pmid: 15142377
references.citation: Annu Rev Immunol. 2001;19:623-55
references.pmid: 11244049
references.citation: N Engl J Med. 2005 Sep 29;353(13):1374-85
references.pmid: 16192482
references.citation: Am J Respir Cell Mol Biol. 2011 Jan;44(1):24-33
references.pmid: 20118223
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3455-60
references.pmid: 19218453
references.citation: PLoS One. 2011 Feb 14;6(2):e14673
references.pmid: 21339814
references.citation: Clin Microbiol Rev. 2007 Apr;20(2):243-67
references.pmid: 17428885
references.citation: J Gen Virol. 2008 Nov;89(Pt 11):2767-2772
references.pmid: 18931074
references.citation: Virology. 2010 Jan 5;396(1):125-34
references.pmid: 19875144
references.citation: J Virol. 2011 Nov;85(21):10955-67
references.pmid: 21865398
references.citation: J Immunol. 2007 Sep 15;179(6):3622-30
references.pmid: 17785797
references.citation: Cell. 2007 Dec 28;131(7):1354-65
references.pmid: 18160043
references.citation: J Virol. 2009 Apr;83(8):3463-74
references.pmid: 19193809
references.citation: J Leukoc Biol. 2010 Dec;88(6):1081-7
references.pmid: 20699362
references.citation: Genomics Proteomics Bioinformatics. 2010 Sep;8(3):139-44
references.pmid: 20970742
references.citation: Pediatr Int. 2005 Apr;47(2):175-9
references.pmid: 15771696
references.citation: J Virol. 2010 Aug;84(16):8332-41
references.pmid: 20534863
references.citation: J Virol. 2010 Aug;84(15):7613-24
references.pmid: 20504916
references.citation: N Engl J Med. 2006 Nov 23;355(21):2186-94
references.pmid: 17124016
references.citation: Vet Pathol. 2010 Sep;47(5):893-914
references.pmid: 20682805
references.citation: Nat Med. 2006 Oct;12(10):1203-7
references.pmid: 16964257
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D322-7
references.pmid: 17098937
references.citation: N Engl J Med. 2008 Jan 17;358(3):261-73
references.pmid: 18199865
references.citation: PLoS One. 2010 Aug 31;5(8):e12465
references.pmid: 20824209
references.citation: J Mol Med (Berl). 2009 Nov;87(11):1053-60
references.pmid: 19705082
references.citation: Am J Physiol. 1994 May;266(5 Pt 1):L493-501
references.pmid: 7515578
references.citation: Genome Res. 2001 Aug;11(8):1425-33
references.pmid: 11483584
references.citation: J Virol. 2006 May;80(10):5041-9
references.pmid: 16641295
references.citation: PLoS Pathog. 2007 Oct 5;3(10):1374-9
references.pmid: 17922570
references.citation: Biochim Biophys Acta. 2011 Jan;1813(1):238-59
references.pmid: 20969895
references.citation: Emerg Infect Dis. 2005 Nov;11(11):1799-1801
references.pmid: 16422010
references.citation: Pac Symp Biocomput. 2011;:314-25
references.pmid: 21121059
references.citation: Apoptosis. 2001 Aug;6(4):253-61
references.pmid: 11445667
references.citation: Transcription. 2010 Nov;1(3):126-129
references.pmid: 21326885
references.citation: Respir Res. 2005 Nov 11;6:135
references.pmid: 16283933
references.citation: PLoS One. 2010 Nov 10;5(11):e13927
references.pmid: 21085662
references.citation: PLoS One. 2009 Dec 14;4(12):e8072
references.pmid: 20011590
references.citation: Respir Res. 2010 Oct 28;11:147
references.pmid: 21029402
references.citation: Genome Biol. 2006;7(5):R36
references.pmid: 16686963
references.citation: Virol J. 2011 Mar 25;8:140
references.pmid: 21439068
references.citation: Immunol Rev. 2008 Oct;225:68-84
references.pmid: 18837776
references.citation: Med Microbiol Immunol. 2009 Aug;198(3):175-83
references.pmid: 19543913
references.citation: Trends Immunol. 2009 Dec;30(12):574-84
references.pmid: 19864182
references.citation: J Virol. 2008 Nov;82(22):11446-53
references.pmid: 18768974
references.citation: Cell Cycle. 2007 Mar 15;6(6):758-66
references.pmid: 17374996
references.citation: Virulence. 2010 Sep-Oct;1(5):436-9
references.pmid: 21178485
references.citation: J Virol. 2007 Mar;81(6):2736-44
references.pmid: 17182684
references.citation: N Engl J Med. 2005 Jan 27;352(4):333-40
references.pmid: 15668219
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10736-41
references.pmid: 12149435