Herpes simplex virus glycoproteins gH/gL and gb Bind Toll-Like Receptor 2, and Soluble gH/gL Is sufficient to activate NF-κB

Valerio Leoni, Tatiana Gianni, Stefano Salvioli, Gabriella Campadelli-Fiume

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

A number of sentinels sense incoming herpes simplex virus (HSV) virions and initiate an immediate innate response. The first line of defense at the cell surface is TLR2 (Toll-like receptor 2), whose signature signaling activity leads to activation of the key transcription factor NF-κB. We report that the HSV pathogen-associated molecular patterns for TLR2 are the virion glycoproteins gH/gL and gB, which constitute the conserved fusion core apparatus across the members of the Herpesviridae family. Specifically, virions devoid singly of one of essential fusion glycoproteins (gD, gB, or gH null), able to attach to cells but defective in fusion/entry, were sufficient to elicit the first wave of NF-κB response to HSV. The most effective were the gD-null virions, positive for gH/gL and gB. A soluble form of gB, truncated upstream of the transmembrane sequence (gB730t-st), was produced in human cells and purified by means of a Strep tag. gH/gL and gB were each able to physically interact with TLR2 in coimmunoprecipitation assays, one independently of the other, yet gHt-st/gL, but not gB730t-st, elicited an NF-κB response. Thus, whereas both HSV gH/gL and gB are ligands to TLR2, only gH/gL is sufficient to initiate a signaling cascade which leads to NF-κB activation.

Original languageEnglish
Pages (from-to)6555-6562
Number of pages8
JournalJournal of Virology
Volume86
Issue number12
DOIs
Publication statusPublished - Jul 2012

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Toll-Like Receptor 2
herpes simplex
Simplexvirus
virion
Virion
glycoproteins
Glycoproteins
viruses
Herpesviridae
cells
Transcription Factors
transcription factors
Ligands
Toll-like receptor 2
pathogens
assays

ASJC Scopus subject areas

  • Immunology
  • Virology

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Herpes simplex virus glycoproteins gH/gL and gb Bind Toll-Like Receptor 2, and Soluble gH/gL Is sufficient to activate NF-κB. / Leoni, Valerio; Gianni, Tatiana; Salvioli, Stefano; Campadelli-Fiume, Gabriella.

In: Journal of Virology, Vol. 86, No. 12, 07.2012, p. 6555-6562.

Research output: Contribution to journalArticle

Leoni, Valerio ; Gianni, Tatiana ; Salvioli, Stefano ; Campadelli-Fiume, Gabriella. / Herpes simplex virus glycoproteins gH/gL and gb Bind Toll-Like Receptor 2, and Soluble gH/gL Is sufficient to activate NF-κB. In: Journal of Virology. 2012 ; Vol. 86, No. 12. pp. 6555-6562.
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