2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models

BMC Genomics

Research Article

Juergen A Richt¹  Wenjun Ma¹  Sarah E Belisle²  Nicolas Tchitchek²  Jennifer T Go²  Michael G Katze³  Terrence M Tumpey⁴  David Safronetz⁵  Heinz Feldmann⁵ 

[1] Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, 66506, Manhattan, KS, USA;Department of Microbiology, University of Washington, 98195, Seattle, WA, USA;Department of Microbiology, University of Washington, 98195, Seattle, WA, USA;Washington National Primate Research Center, University of Washington, 98195, Seattle, WA, USA;Influenza Division, Centers for Disease Control and Prevention, 30333, Atlanta, GA, USA;Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, 59840, Hamilton, MT, USA;

关键词: Pandemic, Influenza virus;    Genomics;    Inflammation;    Lipid metabolism;    Glucocorticoid receptor;    LXR/RXR;   

DOI  :  10.1186/1471-2164-13-627

 received in 2012-07-21, accepted in 2012-11-04,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsDespite 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.ConclusionsBy 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.

【 授权许可】

CC BY   
© Go et al.; licensee BioMed Central Ltd. 2012