2012年8月31日
Integrated network analysis reveals a novel role for the cell cycle in 2009 pandemic influenza virus-induced inflammation in macaque lungs.
BMC systems biology
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- 巻
- 6
- 号
- 開始ページ
- 117
- 終了ページ
- 117
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1186/1752-0509-6-117
- 出版者・発行元
- BIOMED CENTRAL LTD
BACKGROUND: Annually, influenza A viruses circulate the world causing wide-spread sickness, economic loss, and death. One way to better defend against influenza virus-induced disease may be to develop novel host-based therapies, targeted at mitigating viral pathogenesis through the management of virus-dysregulated host functions. However, mechanisms that govern aberrant host responses to influenza virus infection remain incompletely understood. We previously showed that the pandemic H1N1 virus influenza A/California/04/2009 (H1N1; CA04) has enhanced pathogenicity in the lungs of cynomolgus macaques relative to a seasonal influenza virus isolate (A/Kawasaki/UTK-4/2009 (H1N1; KUTK4)). RESULTS: Here, we used microarrays to identify host gene sequences that were highly differentially expressed (DE) in CA04-infected macaque lungs, and we employed a novel strategy - combining functional and pathway enrichment analyses, transcription factor binding site enrichment analysis and protein-protein interaction data - to create a CA04 differentially regulated host response network. This network describes enhanced viral RNA sensing, immune cell signaling and cell cycle arrest in CA04-infected lungs, and highlights a novel, putative role for the MYC-associated zinc finger (MAZ) transcription factor in regulating these processes. CONCLUSIONS: Our findings suggest that the enhanced pathology is the result of a prolonged immune response, despite successful virus clearance. Most interesting, we identify a mechanism which normally suppresses immune cell signaling and inflammation is ineffective in the pH1N1 virus infection; a dyregulatory event also associated with arthritis. This dysregulation offers several opportunities for developing strain-independent, immunomodulatory therapies to protect against future pandemics.
- リンク情報
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- DOI
- https://doi.org/10.1186/1752-0509-6-117
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/22937776
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481363
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000310443200001&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1186/1752-0509-6-117
- ISSN : 1752-0509
- PubMed ID : 22937776
- PubMed Central 記事ID : PMC3481363
- Web of Science ID : WOS:000310443200001