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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >αVβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1
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αVβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1

机译：αVβ3-整联蛋白是单纯疱疹病毒1固有免疫的主要传感器和激活剂。

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摘要

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-kB via this pathway. The other pathway was TLR2-in-dependent, 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 (ICPO) 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.
机译：Toll样受体（TLR）和越来越多的非TLR受体可检测病原体。整联蛋白构成信号传导受体家族，被病毒和细菌利用以进入细胞。通过功能获得和丧失功能的方法，我们发现αVβ3-整联蛋白是先天防御单纯疱疹病毒（HSV）的传感器，并起着至关重要的作用。 αVβ3-整联蛋白通过两个途径发出信号。一个人同意TLR2，影响1型干扰素（IFNs-1），NF-κB（活化的B细胞的核因子κ-轻链增强子）的激活/诱导以及极化的细胞因子和受体集合。病毒体糖蛋白gH / gL足以通过该途径诱导IFN1和NF-kB。另一个途径是TLR2依赖性的，涉及肉瘤（SRC）-脾酪氨酸激酶（SYK）-含Caspase募集域的蛋白质9（CARD9）-TRIF（含TIR域的衔接子诱导干扰素-β），以及影响干扰素调节因子3和7（IRF3-IRF7）。 HSV进化出立即感染的细胞蛋白0（ICPO）蛋白以抵消它的作用，这反映了αVβ3-整合素介导的防御的重要性。我们建议αVβ3-整联蛋白被认为是一类非TLR模式识别受体，它可能对与整联蛋白相互作用并产生先天性应答的病毒和细菌起作用。

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

  • 作者单位

    Department of Experimental Pathology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;

    Department of Experimental Pathology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;

    Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130;

    Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130;

    Department of Experimental Pathology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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