Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway

Virology. 2007 Jun 5;362(2):304-13. doi: 10.1016/j.virol.2006.12.032. Epub 2007 Feb 12.

Abstract

We have previously shown that mutations of CD14 or TLR4 impair type I interferon (IFN) production and macrophage survival during infection with vesicular stomatitis virus (VSV). We now report that VSV glycoprotein G (gpG) is essential for the induction of a previously unrecognized CD14/TLR4-dependent response pathway in which the adapter TRAM has predominant importance, absent any need for MyD88 or Mal, and with only a partial requirement for TRIF. Downstream of TRAM, IRF7 activation leads to a type I IFN response. The pathway is utilized by myeloid dendritic cells (mDCs) and macrophages rather than plasmacytoid DCs. This new mode of TLR4 signal transduction, which does not stimulate NF-kappaB activation, reveals the importance of viral protein recognition by mDCs and shows that TLR4 can drive qualitatively different events within the cell in response to different ligands.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / immunology
  • Animals
  • Cell Line
  • Cell Survival
  • Dendritic Cells / immunology
  • Female
  • Gene Expression Regulation
  • Humans
  • Interferon Regulatory Factor-7 / biosynthesis
  • Interferon Type I / biosynthesis
  • Macrophages, Peritoneal / virology
  • Male
  • Membrane Glycoproteins / immunology*
  • Membrane Transport Proteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Myelin Proteins / immunology
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Myeloid Differentiation Factor 88 / immunology
  • Proteolipids / immunology
  • RNA, Messenger / biosynthesis
  • Receptors, Interleukin / immunology
  • Signal Transduction*
  • Toll-Like Receptor 4 / immunology*
  • Toll-Like Receptor 4 / metabolism
  • Vesicular stomatitis Indiana virus / immunology*
  • Viral Envelope Proteins / immunology*

Substances

  • Adaptor Proteins, Vesicular Transport
  • G protein, vesicular stomatitis virus
  • Interferon Regulatory Factor-7
  • Interferon Type I
  • Irf7 protein, mouse
  • MAL protein, human
  • Mal protein, mouse
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Myd88 protein, mouse
  • Myelin Proteins
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Myeloid Differentiation Factor 88
  • Proteolipids
  • RNA, Messenger
  • Receptors, Interleukin
  • TICAM-1 protein, mouse
  • TIRP protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Viral Envelope Proteins