# The role of heparanase and β-catenin in ocular herpes infection

> **NIH NIH F31** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $42,535

## Abstract

Viral infection leads to the dysregulation and reprogramming of various cellular processes and pathways to
establish a host environment that is suitable for its survival. Published data by our lab show the critical role of
heparanase (HPSE), an endoglycosidase, that participates in the degradation and remodeling of the extracellular
matrix (ECM) through cleavage of heparan sulfate (HS), a proteoglycan expressed on cell surfaces, during the
course of viral infection. Our lab has shown that HPSE expression and activity is upregulated in response to
HSV-1 infection, via NF-kB pathway and, in turn, HPSE facilitates HS shedding from plasma membrane
helping the release of newly generated virions. However, HPSE exhibits non-enzymatic activity as well, and the
involvement of HPSE in the regulation of downstream cellular processes and signal transduction pathways
remains inconclusive. Recent findings by our lab suggest the involvement of both enzymatic and non-enzymatic
HPSE in mediating the activity of β-catenin during viral replication and pathogenesis. Accumulating data
reveals the importance of the β-catenin signal transduction in viral replication, pathogenesis and latency. β-
catenin is an evolutionarily conserved and multifunctional protein involved in the transduction of Wnt signals as
well as intercellular adhesion. The dysregulation of this pathway has been implicated in various pathological
conditions. We have discovered that herpes simplex virus-1 (HSV-1) infection results in wnt-independent
activation, nuclear translocation and signal transduction of β-catenin. Interestingly, inhibiting the binding of β-
catenin with transcriptional coactivators, cAMP response element-binding protein CREB (CBP) and TCF4,
results in robust inhibition of viral replication. However, the differential contributions of β-catenin signal
transduction in primary viral infection and disease progression remains unknown. Given these findings, we
hypothesize that β-catenin-dependent signaling increases viral replication and disease progression and that this
activity is potentiated by HPSE. These hypotheses will be addressed under the following Specific Aims: (1) To
identify the role of HPSE in potentiating β-catenin dependent transcription during HSV-1 infection and (2) To
characterize the role of β-catenin in HSV-1 infection and disease progression. With results gathered from these
studies, we aim to elucidate the differential contributions made by latent and active HPSE in potentiating the
activity of β-catenin during HSV-1 infection, identify key pathways that β-catenin signal transduction may
influence and expose key therapeutic targets in the treatment of ocular HSV-1.

## Key facts

- **NIH application ID:** 10146532
- **Project number:** 1F31EY031568-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Lulia Koujah
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $42,535
- **Award type:** 1
- **Project period:** 2021-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146532

## Citation

> US National Institutes of Health, RePORTER application 10146532, The role of heparanase and β-catenin in ocular herpes infection (1F31EY031568-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10146532. Licensed CC0.

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