αvβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1

Tatiana Gianni, Valerio Leoni, Liudmila S. Chesnokova, Lindsey M. Hutt-Fletcher, Gabriella Campadelli-Fiume

Research output: Contribution to journalArticle

Abstract

Pathogens are sensed by Toll-like receptors (TLRs) and a growing number of non-TLR receptors. Integrins constitute a family of signaling receptors exploited by viruses and bacteria to access cells. By gainand loss-of-function approaches we found that αvβ3-integrin is a sensor of and plays a crucial role in the innate defense against herpes simplex virus (HSV). αvβ3-integrin signaled through two pathways. One concurred with TLR2, affected activation/induction of interferons type 1 (IFNs-1), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and a polarized set of cytokines and receptors. The virion glycoproteins gH/gL sufficed to induce IFN1 and NF-κB via this pathway. The other pathway was TLR2-independent, involved sarcoma (SRC)-spleen tyrosine kinase (SYK)-Caspase recruitment domain-containing protein 9 (CARD9)-TRIF (TIR-domain-containing adapter-inducing interferon-β), and affected interferon regulatory factor 3 and 7 (IRF3-IRF7). The importance of αvβ3-integrin-mediated defense is reflected in the observation that HSV evolved the immediate-early infected cellular protein 0 (ICP0) protein to counteract it. We propose that αvβ3-integrin is considered a class of non-TLR pattern recognition receptors, a role likely exerted toward viruses and bacteria that interact with integrins and mount an innate response.

Original languageEnglish
Pages (from-to)19792-19797
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number48
DOIs
Publication statusPublished - Nov 27 2012

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Human Herpesvirus 1
Innate Immunity
Integrins
Simplexvirus
Interferon Regulatory Factor-7
Interferon Regulatory Factor-3
Bacteria
Virus Receptors
Pattern Recognition Receptors
Interferon Type I
Proteins
Cytokine Receptors
NF-kappa B
Toll-Like Receptors
Sarcoma
Virion
Interferons
Glycoproteins
B-Lymphocytes
Viruses

ASJC Scopus subject areas

  • General

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αvβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1. / Gianni, Tatiana; Leoni, Valerio; Chesnokova, Liudmila S.; Hutt-Fletcher, Lindsey M.; Campadelli-Fiume, Gabriella.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 48, 27.11.2012, p. 19792-19797.

Research output: Contribution to journalArticle

Gianni, Tatiana ; Leoni, Valerio ; Chesnokova, Liudmila S. ; Hutt-Fletcher, Lindsey M. ; Campadelli-Fiume, Gabriella. / αvβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 48. pp. 19792-19797.
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