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 language | English |
|---|---|
| Pages (from-to) | 6555-6562 |
| Number of pages | 8 |
| Journal | Journal of Virology |
| Volume | 86 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Jul 2012 |
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ASJC Scopus subject areas
- Immunology
- Virology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Herpes simplex virus glycoproteins gH/gL and gb Bind Toll-Like Receptor 2, and Soluble gH/gL Is sufficient to activate NF-κB
AU - Leoni, Valerio
AU - Gianni, Tatiana
AU - Salvioli, Stefano
AU - Campadelli-Fiume, Gabriella
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84864010826&partnerID=8YFLogxK
U2 - 10.1128/JVI.00295-12
DO - 10.1128/JVI.00295-12
M3 - Article
C2 - 22496225
AN - SCOPUS:84864010826
VL - 86
SP - 6555
EP - 6562
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 12
ER -