Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1

Publication date: 11 July 2017
Source:Cell Reports, Volume 20, Issue 2
Author(s): Alex M. Agelidis, Satvik R. Hadigal, Dinesh Jaishankar, Deepak Shukla
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.

Graphical abstract

Teaser

Agelidis et al. demonstrate that herpes simplex virus-1 (HSV-1) infection activates the host protein heparanase (HPSE), which drives key processes in herpes pathogenesis. These results shed light on the mechanisms by which HSV-1 disrupts homeostasis and breaks immune tolerance in the case of the human cornea.


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