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Tumor necrosis factor alpha enhances influenza A virus-induced expression of antiviral cytokines by activating RIG-I gene expression.
J Virol 2006; 80(7):3515-22JV

Abstract

Epithelial cells of the lung are the primary targets for respiratory viruses. Virus-carried single-stranded RNA (ssRNA) can activate Toll-like receptors (TLRs) 7 and 8, whereas dsRNA is bound by TLR3 and a cytoplasmic RNA helicase, retinoic acid-inducible protein I (RIG-I). This recognition leads to the activation of host cell cytokine gene expression. Here we have studied the regulation of influenza A and Sendai virus-induced alpha interferon (IFN-alpha), IFN-beta, interleukin-28 (IL-28), and IL-29 gene expression in human lung A549 epithelial cells. Sendai virus infection readily activated the expression of the IFN-alpha, IFN-beta, IL-28, and IL-29 genes, whereas influenza A virus-induced activation of these genes was mainly dependent on pretreatment of A549 cells with IFN-alpha or tumor necrosis factor alpha (TNF-alpha). IFN-alpha and TNF-alpha induced the expression of the RIG-I, TLR3, MyD88, TRIF, and IRF7 genes, whereas no detectable TLR7 and TLR8 was seen in A549 cells. TNF-alpha also strongly enhanced IKK epsilon mRNA and protein expression. Ectopic expression of a constitutively active form of RIG-I (deltaRIG-I) or IKK epsilon, but not that of TLR3, enhanced the expression of the IFN-beta, IL-28, and IL-29 genes. Furthermore, a dominant-negative form of RIG-I inhibited influenza A virus-induced IFN-beta promoter activity in TNF-alpha-pretreated cells. In conclusion, IFN-alpha and TNF-alpha enhanced the expression of the components of TLR and RIG-I signaling pathways, but RIG-I was identified as the central regulator of influenza A virus-induced expression of antiviral cytokines in human lung epithelial cells.

Authors+Show Affiliations

Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland. sampsa.matikainen@ttl.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16537619

Citation

Matikainen, Sampsa, et al. "Tumor Necrosis Factor Alpha Enhances Influenza a Virus-induced Expression of Antiviral Cytokines By Activating RIG-I Gene Expression." Journal of Virology, vol. 80, no. 7, 2006, pp. 3515-22.
Matikainen S, Sirén J, Tissari J, et al. Tumor necrosis factor alpha enhances influenza A virus-induced expression of antiviral cytokines by activating RIG-I gene expression. J Virol. 2006;80(7):3515-22.
Matikainen, S., Sirén, J., Tissari, J., Veckman, V., Pirhonen, J., Severa, M., ... Julkunen, I. (2006). Tumor necrosis factor alpha enhances influenza A virus-induced expression of antiviral cytokines by activating RIG-I gene expression. Journal of Virology, 80(7), pp. 3515-22.
Matikainen S, et al. Tumor Necrosis Factor Alpha Enhances Influenza a Virus-induced Expression of Antiviral Cytokines By Activating RIG-I Gene Expression. J Virol. 2006;80(7):3515-22. PubMed PMID: 16537619.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor alpha enhances influenza A virus-induced expression of antiviral cytokines by activating RIG-I gene expression. AU - Matikainen,Sampsa, AU - Sirén,Jukka, AU - Tissari,Jorma, AU - Veckman,Ville, AU - Pirhonen,Jaana, AU - Severa,Martina, AU - Sun,Qiang, AU - Lin,Rongtuan, AU - Meri,Seppo, AU - Uzé,Gilles, AU - Hiscott,John, AU - Julkunen,Ilkka, PY - 2006/3/16/pubmed PY - 2006/4/14/medline PY - 2006/3/16/entrez SP - 3515 EP - 22 JF - Journal of virology JO - J. Virol. VL - 80 IS - 7 N2 - Epithelial cells of the lung are the primary targets for respiratory viruses. Virus-carried single-stranded RNA (ssRNA) can activate Toll-like receptors (TLRs) 7 and 8, whereas dsRNA is bound by TLR3 and a cytoplasmic RNA helicase, retinoic acid-inducible protein I (RIG-I). This recognition leads to the activation of host cell cytokine gene expression. Here we have studied the regulation of influenza A and Sendai virus-induced alpha interferon (IFN-alpha), IFN-beta, interleukin-28 (IL-28), and IL-29 gene expression in human lung A549 epithelial cells. Sendai virus infection readily activated the expression of the IFN-alpha, IFN-beta, IL-28, and IL-29 genes, whereas influenza A virus-induced activation of these genes was mainly dependent on pretreatment of A549 cells with IFN-alpha or tumor necrosis factor alpha (TNF-alpha). IFN-alpha and TNF-alpha induced the expression of the RIG-I, TLR3, MyD88, TRIF, and IRF7 genes, whereas no detectable TLR7 and TLR8 was seen in A549 cells. TNF-alpha also strongly enhanced IKK epsilon mRNA and protein expression. Ectopic expression of a constitutively active form of RIG-I (deltaRIG-I) or IKK epsilon, but not that of TLR3, enhanced the expression of the IFN-beta, IL-28, and IL-29 genes. Furthermore, a dominant-negative form of RIG-I inhibited influenza A virus-induced IFN-beta promoter activity in TNF-alpha-pretreated cells. In conclusion, IFN-alpha and TNF-alpha enhanced the expression of the components of TLR and RIG-I signaling pathways, but RIG-I was identified as the central regulator of influenza A virus-induced expression of antiviral cytokines in human lung epithelial cells. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/16537619/Tumor_necrosis_factor_alpha_enhances_influenza_A_virus_induced_expression_of_antiviral_cytokines_by_activating_RIG_I_gene_expression_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=16537619 DB - PRIME DP - Unbound Medicine ER -