title: αvβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1.
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 gain- and 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.
authors.affiliation: Department of Experimental Pathology,  Alma Mater Studiorum-University of Bologna, 40126 Bologna,  Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gianni
authors.forename: Valerio
authors.initials: V
authors.lastname: Leoni
authors.forename: Liudmila S
authors.initials: LS
authors.lastname: Chesnokova
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Hutt-Fletcher
authors.forename: Gabriella
authors.initials: G
authors.lastname: Campadelli-Fiume
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D020868:Gene Silencing; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014779:Virus Replication
chemical_list: D016207:Cytokines; D039302:Integrin alphaVbeta3; D016328:NF-kappa B