PMID- 16051830
OWN - NLM
STAT- MEDLINE
DCOM- 20050908
LR  - 20240411
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 79
IP  - 16
DP  - 2005 Aug
TI  - 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.
PG  - 10376-85
AB  - 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.
FAU - Hidmark, Asa S
AU  - Hidmark AS
AD  - Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 
      Stockholm, Sweden.
FAU - McInerney, Gerald M
AU  - McInerney GM
FAU - Nordstrom, Eva K L
AU  - Nordstrom EK
FAU - Douagi, Iyadh
AU  - Douagi I
FAU - Werner, Kristen M
AU  - Werner KM
FAU - Liljestrom, Peter
AU  - Liljestrom P
FAU - Karlsson Hedestam, Gunilla B
AU  - Karlsson Hedestam GB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Interferon-alpha)
RN  - 0 (Irf3 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Transcription Factors)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, Differentiation/*physiology
MH  - Cricetinae
MH  - DNA-Binding Proteins/*physiology
MH  - Dendritic Cells/*metabolism
MH  - Hydrogen-Ion Concentration
MH  - Interferon Regulatory Factor-3
MH  - Interferon-alpha/*biosynthesis
MH  - Interferon-beta/*biosynthesis
MH  - Membrane Fusion
MH  - Membrane Glycoproteins/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Cells/*metabolism
MH  - Myeloid Differentiation Factor 88
MH  - Receptors, Cell Surface/physiology
MH  - Receptors, Immunologic/*physiology
MH  - Semliki forest virus/*physiology/radiation effects
MH  - Toll-Like Receptors
MH  - Transcription Factors/*physiology
MH  - Ultraviolet Rays
MH  - Virus Replication
PMC - PMC1182635
EDAT- 2005/07/30 09:00
MHDA- 2005/09/09 09:00
PMCR- 2005/08/01
CRDT- 2005/07/30 09:00
PHST- 2005/07/30 09:00 [pubmed]
PHST- 2005/09/09 09:00 [medline]
PHST- 2005/07/30 09:00 [entrez]
PHST- 2005/08/01 00:00 [pmc-release]
AID - 79/16/10376 [pii]
AID - 0292-05 [pii]
AID - 10.1128/JVI.79.16.10376-10385.2005 [doi]
PST - ppublish
SO  - J Virol. 2005 Aug;79(16):10376-85. doi: 10.1128/JVI.79.16.10376-10385.2005.