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

ABSTRACT: 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.

SUBMITTER: Agelidis AM

PROVIDER: S-EPMC5557421 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Agelidis Alex M AM Hadigal Satvik R SR Jaishankar Dinesh D Shukla Deepak D

Cell reports 20170701 2

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, i ...[more]

PMID: 28700944

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Dataset Information

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

Publications

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

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