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

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.

Keywords: cornea; cytokines; heparan sulfate; heparanase; herpes simplex virus; inflammation; interferon; ophthalmology; transcription factors; wound healing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Female
  • Flow Cytometry
  • Glucuronidase / metabolism*
  • HeLa Cells
  • Herpes Simplex / metabolism
  • Herpesvirus 1, Human / pathogenicity*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Fluorescence
  • Virus Activation / physiology*
  • Wound Healing / physiology


  • heparanase
  • Glucuronidase