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

Philippe Georgel, Zhengfan Jiang, Stefan Kunz, Edith Janssen, Johann Mols, Kasper Hoebe, Siamak Bahram, Michael B A Oldstone, Bruce Beutler

Research output: Contribution to journalArticle

136 Scopus citations

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-κB 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.

Original languageEnglish (US)
Pages (from-to)304-313
Number of pages10
JournalVirology
Volume362
Issue number2
DOIs
StatePublished - Jun 5 2007

Keywords

  • Antiviral
  • Immunity
  • Innate
  • Interferon
  • TLR
  • VSV

ASJC Scopus subject areas

  • Virology

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    Georgel, P., Jiang, Z., Kunz, S., Janssen, E., Mols, J., Hoebe, K., Bahram, S., Oldstone, M. B. A., & Beutler, B. (2007). Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway. Virology, 362(2), 304-313. https://doi.org/10.1016/j.virol.2006.12.032