# Therapeutic control of HSK by CD80

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2021 · $417,500

## Abstract

Project Summary
 Following ocular primary herpes simplex virus type-1 (HSV-1) infection, the virus replicates in the eye
and establishes latency in the trigeminal ganglia (TG). In a latently infected individual, the virus can
occasionally reactivate and travel back to the eye causing recurrent disease. This reactivation from latency is
the major cause of corneal scarring (CS) in HSV-1 eye infections. We have shown previously that elicitation of
neutralizing antibody alone can protect immunized mice from eye disease and death; however, it does not
protect the immunized mice from virus replication in the eye and the establishment of latency in the TG. We
therefore focused on the mechanisms by which HSV-1 may subvert the ability of the immune system to clear
the virus, limit viral load, and prevent establishment of latency. We have shown that HSV-1 viral ICP22
suppresses the host CD80 co-stimulatory molecule and that this leads to reduced CD8+ CTL activity in the eye
and TG of ocularly infected mice, which in turn leads to less effective and delayed clearance of virus and
increased susceptibility to establishment of latency but at the same time protect host from HSV-1-induced
pathology. Our published and preliminary studies identified immune response regulatory mechanisms that
could be targeted to enhance the vaccine’s ability to reduce HSV-1 replication in the eye and prevent latency-
reactivation. By completing these studies, we expect to identify a novel approach to generating a vaccine with
both prophylactic and therapeutic applications that may control acute and latent infection without adverse
effects. This will be achieved by understanding how ICP22 and CD80 coordinately regulate virus replication in
the eye, eye disease, and latency-reactivation. Collectively, our Specific Aims focus on understanding
mechanisms of immune escape that protect the host from increased pathology while reducing viral clearance.
We propose to: (1) Determine whether blocking binding of ICP22 to the CD80 promoter will increase primary
HSV-1 infection, latency-reactivation, and eye disease in ocularly infected mice; and (2) Determine whether
exacerbation of CS by a recombinant HSV-1 expressing CD80 (HSV-CD80) or by viruses lacking the ICP22
suppressive effect is associated with the presence of PD-L1 but not CD28 or CTLA4.
CLINICAL SIGNIFICANCE: HSV-1 infections are among the most frequent serious viral eye infections in the
U.S. and are a major cause of viral-induced blindness. The results generated by this study will potentially
establish a previously undescribed mechanism underlying viral immune evasion that could be exploited to
better manage HSV infection. In light of recent failure of a large-scale phase III HSV-1 vaccine trials, our
approach may help design a more efficacious vaccine.

## Key facts

- **NIH application ID:** 10141893
- **Project number:** 2R01EY026944-05
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** HOMAYON GHIASI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $417,500
- **Award type:** 2
- **Project period:** 2016-09-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141893

## Citation

> US National Institutes of Health, RePORTER application 10141893, Therapeutic control of HSK by CD80 (2R01EY026944-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141893. Licensed CC0.

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