Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines.

Abstract

Activation of host cell antiviral responses is mediated by pattern recognition receptors. Cytoplasmic RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (mda-5) have been identified to function as receptors for double-stranded RNA. Here we show that interferon (IFN)-alpha pretreatment enhances influenza A virus-induced expression of IFN-alpha, IFN-beta, interleukin (IL)-28 and IL-29 genes in human dendritic cells and epithelial cell lines. Both IFN-alpha and IFN-beta strongly enhanced RIG-I and mda-5 mRNA and protein expression in these cell types. Expression of RIG-I and mda-5 gene constructs, but not that of TLR3, lead to a dramatic enhancement of IFN-beta promoter driven transcription in influenza A virus-infected epithelial cells. Furthermore, dominant negative RIG-I gene construct inhibited influenza A virus-induced IFN-beta promoter activity. In conclusion, our results show that in epithelial cells influenza A virus-induced antiviral cytokine gene expression is triggered by RIG-I and mda-5, whose expression is positively regulated by IFN-alpha.

• Authors: Jukka Sirén, Tadaatsu Imaizumi, Devanand Sarkar, Taija Pietilä, Diana L Noah, Rongtuan Lin, John Hiscott, Robert M Krug, Paul B Fisher, Ilkka Julkunen, Sampsa Matikainen
• Journal: Microbes and infection (Microbes Infect) Vol. 8 Issue 8 Pg. 2013-20 (Jul 2006) ISSN: 1286-4579 [Print] France
• PMID: 16797201 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Proteins
• RAI1 protein, human
• RNA, Messenger
• Trans-Activators
• Transcription Factors
• IFIH1 protein, human
• DEAD-box RNA Helicases
• Interferon-Induced Helicase, IFIH1

Topics

• Cytokines (biosynthesis)
• DEAD-box RNA Helicases (physiology)
• Dendritic Cells (immunology, virology)
• Epithelial Cells (immunology, virology)
• Gene Expression Regulation
• Humans
• Influenza A Virus, H3N2 Subtype (immunology)
• Influenza A virus (immunology)
• Interferon-Induced Helicase, IFIH1
• Proteins (analysis)
• RNA, Messenger (analysis)
• Trans-Activators
• Transcription Factors (physiology)