?v?3-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 ?v?3-integrin is a sensor of and plays a crucial role in the innate defense against herpes simplex virus (HSV). ?v?3-integrin signaled through two pathways. One concurred with TLR2, affected activation/induction of interferons type 1 (IFNs-1), NF-?B (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-?B 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-?), and affected interferon regulatory factor 3 and 7 (IRF3-IRF7). The importance of ?v?3-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 ?v?3-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.

SUBMITTER: Gianni T 

PROVIDER: S-EPMC3511702 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature