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

Alex M. Agelidis, Satvik R. Hadigal, Dinesh Jaishankar, Deepak Shukla*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)439-450
Number of pages12
JournalCell reports
Issue number2
StatePublished - Jul 11 2017
Externally publishedYes


  • cornea
  • cytokines
  • heparan sulfate
  • heparanase
  • herpes simplex virus
  • inflammation
  • interferon
  • ophthalmology
  • transcription factors
  • wound healing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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