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Journal of Virology, August 2005, p. 9608-9617, Vol. 79, No. 15
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.15.9608-9617.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Gene Expression and Antiviral Activity of Alpha/Beta Interferons and Interleukin-29 in Virus-Infected Human Myeloid Dendritic Cells
Pamela Österlund,1
Ville Veckman,1
Jukka Sirén,1
Kevin M. Klucher,2
John Hiscott,3
Sampsa Matikainen,1 and
Ilkka Julkunen1*
Department of Viral Diseases and Immunology, National Public Health Institute, FIN-00300 Helsinki, Finland,1
ZymoGenetics, Inc., Eastlake Ave. E., Seattle, Washington 98102,2
Lady Davis Institute for Medical Research and Departments of Microbiology and Immunology & Medicine, McGill University, Montreal, Quebec, Canada H3T 1E23
Received 5 January 2005/
Accepted 19 April 2005
Dendritic cells (DCs) respond to microbial infections by undergoing phenotypic maturation and by producing multiple cytokines. In the present study, we analyzed the ability of influenza A and Sendai viruses to induce DC maturation and activate tumor necrosis factor alpha (TNF-
), alpha/beta interferon (IFN-
/ß), and IFN-like interleukin-28A/B (IFN-
2/3) and IL-29 (IFN-
1) gene expression in human monocyte-derived myeloid DCs (mDC). The ability of influenza A virus to induce mDC maturation or enhance the expression of TNF-
, IFN-
/ß, interleukin-28 (IL-28), and IL-29 genes was limited, whereas Sendai virus efficiently induced mDC maturation and enhanced cytokine gene expression. Influenza A virus-induced expression of TNF-
, IFN-
, IFN-ß, IL-28, and IL-29 genes was, however, dramatically enhanced when cells were pretreated with IFN-
. IFN-
priming led to increased expression of Toll-like receptor 3 (TLR3), TLR7, TLR8, MyD88, TRIF, and IFN regulatory factor 7 (IRF7) genes and enhanced influenza-induced phosphorylation and DNA binding of IRF3. Influenza A virus also enhanced the binding of NF-
B to the respective NF-
B elements of the promoters of IFN-ß and IL-29 genes. In mDC IL-29 induced MxA protein expression and possessed antiviral activity against influenza A virus, although this activity was lower than that of IFN-
or IFN-ß. Our results show that in human mDCs viruses can readily induce the expression of IL-28 and IL-29 genes whose gene products are likely to contribute to the host antiviral response.
* Corresponding author. Mailing address: Department of Viral Diseases and Immunology, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. Phone: 358-9-47448372. Fax: 358-9-47448355. E-mail:
ilkka.julkunen{at}ktl.fi.
Journal of Virology, August 2005, p. 9608-9617, Vol. 79, No. 15
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.15.9608-9617.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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