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

doi:10.1016/j.virol.2006.12.032

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 journal › Article › peer-review

163 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 language	English (US)
Pages (from-to)	304-313
Number of pages	10
Journal	Virology
Volume	362
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2006.12.032
State	Published - Jun 5 2007

Keywords

Antiviral
Immunity
Innate
Interferon
TLR
VSV

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2006.12.032

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

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.",

keywords = "Antiviral, Immunity, Innate, Interferon, TLR, VSV",

author = "Philippe Georgel and Zhengfan Jiang and Stefan Kunz and Edith Janssen and Johann Mols and Kasper Hoebe and Siamak Bahram and Oldstone, {Michael B A} and Bruce Beutler",

note = "Funding Information: This work was supported by the NIH, Grant AI054523. PG was supported by an EMBO short-term fellowship and acknowledges financial support from la Ligue contre le cancer and Fondation pour la Recherche M{\'e}dicale.",

year = "2007",

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doi = "10.1016/j.virol.2006.12.032",

language = "English (US)",

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AU - Georgel, Philippe

AU - Jiang, Zhengfan

AU - Kunz, Stefan

AU - Janssen, Edith

AU - Mols, Johann

AU - Hoebe, Kasper

AU - Bahram, Siamak

AU - Oldstone, Michael B A

AU - Beutler, Bruce

N1 - Funding Information: This work was supported by the NIH, Grant AI054523. PG was supported by an EMBO short-term fellowship and acknowledges financial support from la Ligue contre le cancer and Fondation pour la Recherche Médicale.

PY - 2007/6/5

Y1 - 2007/6/5

N2 - 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.

AB - 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.

KW - Antiviral

KW - Immunity

KW - Innate

KW - Interferon

KW - TLR

KW - VSV

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

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Keywords

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