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PMID: 16051830 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Early alpha/beta interferon production by myeloid dendritic cells in response to UV-inactivated virus requires viral entry and interferon regulatory factor 3 but not MyD88.

Journal of virology ·Vol. 79 ·No. 16 ·2005-08-00 ·Pages 10376-85

Hidmark AS, McInerney GM, Nordström EK, Douagi I, Werner KM, Liljeström P, Karlsson Hedestam GB

Abstract

Alpha/beta interferons (IFN-alpha/beta) are key mediators of innate immunity and important modulators of adaptive immunity. The mechanisms by which IFN-alpha/beta are induced are becoming increasingly well understood. Recent studies showed that Toll-like receptors 7 and 8 expressed by plasmacytoid dendritic cells (pDCs) mediate the endosomal recognition of incoming viral RNA genomes, a process which requires myeloid differentiation factor 88 (MyD88). Here we investigate the requirements for virus-induced IFN-alpha/beta production in cultures of bone marrow-derived murine myeloid DCs (mDCs). Using recombinant Semliki Forest virus blocked at different steps in the viral life cycle, we show that replication-defective virus induced IFN-alpha/beta in mDCs while fusion-defective virus did not induce IFN-alpha/beta. The response to replication-defective virus was largely intact in MyD88-/- mDC cultures but was severely reduced in mDC cultures from mice lacking IFN regulatory factor 3. Our observations suggest that mDCs respond to incoming virus via a pathway that differs from the fusion-independent, MyD88-mediated endosomal pathway described for the induction of IFN-alpha/beta in pDCs. We propose that events during or downstream of viral fusion, but prior to replication, can activate IFN-alpha/beta in mDCs. Thus, mDCs may contribute to the antiviral response activated by the immune system at early time points after infection.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Antigens, Differentiation/physiology Cricetinae DNA-Binding Proteins/physiology Dendritic Cells/metabolism Hydrogen-Ion Concentration Interferon Regulatory Factor-3 Interferon-alpha/biosynthesis Interferon-beta/biosynthesis Membrane Fusion Membrane Glycoproteins/physiology Mice Mice, Inbred C57BL Myeloid Cells/metabolism Myeloid Differentiation Factor 88 Receptors, Cell Surface/physiology Receptors, Immunologic/physiology Semliki forest virus/physiology,radiation effects Toll-Like Receptors Transcription Factors/physiology Ultraviolet Rays Virus Replication
Chemicals
Adaptor Proteins, Signal Transducing Antigens, Differentiation DNA-Binding Proteins Interferon Regulatory Factor-3 Interferon-alpha Irf3 protein, mouse Membrane Glycoproteins Myd88 protein, mouse Myeloid Differentiation Factor 88 Receptors, Cell Surface Receptors, Immunologic Toll-Like Receptors Transcription Factors Interferon-beta
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hidmark Asa S
Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden.
McInerney Gerald M
Nordström Eva K L
Douagi Iyadh
Werner Kristen M
Liljeström Peter
Karlsson Hedestam Gunilla B
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.16.10376-10385.2005
Published
2005-08-00
Pages
10376-85
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1182635
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.79.16.10376-10385.2005 PMC Full Text View journal details
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