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

J Virol. 2005 Aug;79(16):10376-85. doi: 10.1128/JVI.79.16.10376-10385.2005.


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.

Publication types

  • Research Support, Non-U.S. Gov't

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*
  • Semliki forest virus / radiation effects
  • Toll-Like Receptors
  • Transcription Factors / physiology*
  • Ultraviolet Rays
  • Virus Replication


  • 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