# HPSE in Ocular Herpes Infection

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $422,753

## Abstract

From the previous R01 funding period we have generated compelling new evidence that human Heparanase-1
(HPSE), a heparan sulfate (HS) endoglycosidase, is a virulence factor responsible for triggering angiogenesis
and inflammation in the eye during herpes simplex virus type-1 (HSV-1) infection. Our in vivo studies have shown
that HPSE presence can significantly increase HSV-1 replication and severity of ocular disease with poor
prognosis. Investigation of transcriptional and proteomic landscapes revealed a multitude of non-enzymatic roles
for HPSE during HSV-1 infection and identified new druggable targets. Upon further investigation, we found that
the significance of HPSE in corneal infection may not be limited to promoting viral pathogenesis only, but also in
the induction of inflammatory cell death in a protein kinase B (Akt) dependent manner. Making things even more
interesting and potentially more significant, our new preliminary data suggests that HPSE and Akt2 isoform
phenocopy each other both in inflammatory cell death and deficiency in virus production. Therefore, based on
our published observations of HPSE’s non-enzymatic roles and preliminary results, we hypothesize an important,
yet interconnected regulatory role for HPSE and Akt2 in HSV-1 mediated ocular inflammation, nerve damage,
and the resultant vision loss. We propose that their inhibition through small molecules can reduce disease
severity and viral replication in the eye and reduce the incidences of viral encephalitis. This proposal will focus
on understanding HPSE driven inflammatory cell death mechanisms and the role for Akt2 during HSV-1
replication, spread and disease pathology in the cornea. Successful completion of our studies will identify new
and more effective HPSE and Akt2 inhibitors that can reduce inflammation as well as virus load without causing
any adverse effects. Results generated through the proposed experiments will be broadly relevant, as aberrant
HPSE activity has been implicated in a wide array of ocular pathologies and other neurodegenerative diseases
and disorders such as multiple sclerosis and Alzheimer’s Disease.

## Key facts

- **NIH application ID:** 10914258
- **Project number:** 5R01EY029426-07
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** DEEPAK SHUKLA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $422,753
- **Award type:** 5
- **Project period:** 2018-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914258

## Citation

> US National Institutes of Health, RePORTER application 10914258, HPSE in Ocular Herpes Infection (5R01EY029426-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10914258. Licensed CC0.

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