title: 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models.
abstract: BACKGROUND
  The 2009 pandemic H1N1 influenza virus emerged in swine and quickly became a major global health threat. In mouse, non human primate, and swine infection models, the pH1N1 virus efficiently replicates in the lung and induces pro-inflammatory host responses; however, whether similar or different cellular pathways were impacted by pH1N1 virus across independent infection models remains to be further defined. To address this we have performed a comparative transcriptomic analysis of acute phase responses to a single pH1N1 influenza virus, A/California/04/2009 (CA04), in the lung of mice, macaques and swine.
  
  
  RESULTS
  Despite similarities in the clinical course, we observed differences in inflammatory molecules elicited, and the kinetics of their gene expression changes across all three species. We found genes associated with the retinoid X receptor (RXR) signaling pathway known to control pro-inflammatory and metabolic processes that were differentially regulated during infection in each species, though the heterodimeric RXR partner, pathway associated signaling molecules, and gene expression patterns varied among the three species.
  
  
  CONCLUSIONS
  By comparing transcriptional changes in the context of clinical and virological measures, we identified differences in the host transcriptional response to pH1N1 virus across independent models of acute infection. Antiviral resistance and the emergence of new influenza viruses have placed more focus on developing drugs that target the immune system. Underlying overt clinical disease are molecular events that suggest therapeutic targets identified in one host may not be appropriate in another.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, 98195, USA. tisoncik@u.washington.edu
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Go
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Belisle
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tchitchek
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Richt
authors.forename: David
authors.initials: D
authors.lastname: Safronetz
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008251:Macaca; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000662:veterinary* / Q000821:virology; D058873:Pandemics; D055503:Protein Multimerization; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D059467:Transcriptome
chemical_list: D047488:Retinoid X Receptors