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.
Philippe Georgel  1 ,  Zhengfan Jiang ,  Stefan Kunz ,  Edith Janssen ,  Johann Mols ,  Kasper Hoebe ,  Siamak Bahram ,  Michael B A Oldstone ,  Bruce Beutler
Affiliations
  • 1. Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. [email protected]
PMID: 17292937 DOI: 10.1016/j.virol.2006.12.032
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.