Agelidis Alex M, Hadigal Satvik R, Jaishankar Dinesh, Shukla Deepak
Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, IL 60612, USA; Department of Microbiology and Immunology, College of Medicine, E-704 Medical Sciences Building, University of Illinois at Chicago, 835 South Wolcott Avenue, M/C 790, Chicago, IL 60612, USA.
Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, IL 60612, USA.
Cell Rep. 2017 Jul 11;20(2):439-450. doi: 10.1016/j.celrep.2017.06.041.
Herpes simplex virus-1 (HSV-1) causes lifelong recurrent pathologies without a cure. How infection by HSV-1 triggers disease processes, especially in the immune-privileged avascular human cornea, remains a major unresolved puzzle. It has been speculated that a cornea-resident molecule must tip the balance in favor of pro-inflammatory and pro-angiogenic conditions observed with herpetic, as well as non-herpetic, ailments of the cornea. Here, we demonstrate that heparanase (HPSE), a host enzyme, is the molecular trigger for multiple pathologies associated with HSV-1 infection. In human corneal epithelial cells, HSV-1 infection upregulates HPSE in a manner dependent on HSV-1 infected cell protein 34.5. HPSE then relocates to the nucleus to regulate cytokine production, inhibits wound closure, enhances viral spread, and thus generates a toxic local environment. Overall, our findings implicate activated HPSE as a driver of viral pathogenesis and call for further attention to this host protein in infection and other inflammatory disorders.
单纯疱疹病毒1型（HSV-1）会引发终身复发性病变，且无法治愈。HSV-1感染如何引发疾病进程，尤其是在免疫赦免的无血管人角膜中，仍是一个主要的未解之谜。据推测，一种角膜驻留分子必定会打破平衡，有利于在疱疹性以及非疱疹性角膜疾病中观察到的促炎和促血管生成状态。在此，我们证明，宿主酶乙酰肝素酶（HPSE）是与HSV-1感染相关的多种病变的分子触发因素。在人角膜上皮细胞中，HSV-1感染以依赖HSV-1感染细胞蛋白34.5的方式上调HPSE。然后，HPSE重新定位到细胞核以调节细胞因子的产生，抑制伤口愈合，增强病毒传播，从而产生有毒的局部环境。总体而言，我们的研究结果表明活化的HPSE是病毒发病机制的驱动因素，并呼吁在感染和其他炎症性疾病中进一步关注这种宿主蛋白。
