# Neurovirulence determinants of neonatal HSV disease

> **NIH NIH K08** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2021 · $191,159

## Abstract

Project Summary
This proposal describes a five-year training plan for the development of an independent research career
focused on the virus-host interactions that dictate susceptibility of the pediatric brain to infection. Specifically,
the applicant strives to elucidate how viral genetic variation influences neurovirulence, both by altering viral
function and inducing immune escape. The applicant is an attending Infectious Diseases physician at the
Children's Hospital of Philadelphia (CHOP) with previous PhD training in basic neuroimmunology. The goals
for this award are to develop and refine the essential skills that will be required for a successful career as an
independent investigator, including expertise in sequencing and bioinformatic analysis of large genetic data
sets, viral genome editing, and neurologically-relevant in vitro and in vivo models of viral infection. The mentors
for this award include Dr. Matthew Weitzman, an internationally recognized leader in the field of virus-host
interactions, and Dr. Dennis Kolson, a physician-scientist and expert in mechanisms of neurovirulence. To add
depth and breadth to the scientific career guidance of the applicant, a scientific advisory committee is
composed of scientists and physician-scientists from diverse and complementary fields. Dr. Akhtar will also
benefit from the unparalleled resources and mentorship available at both CHOP and the University of
Pennsylvania.
The proposed research focuses on the role of viral genetic variability in determining the clinical manifestations
of neonatal herpes simplex virus (HSV) disease, particularly the ability to infect the neonatal brain. HSV
infection of the neonatal brain causes severe encephalitis and permanent neurologic deficits, but the factors
that promote central nervous system (CNS) infection are not known. Recent studies show that substantial
genetic variability exists within HSV genomes, but have not evaluated how these variations impact viral growth
characteristics or human disease manifestations. Successful completion of the studies proposed will identify
HSV genetic variations associated with neonatal CNS disease, determine their impact on viral spread between
neurons, and their ability to alter progression to CNS infection. This will be accomplished by large-scale viral
genomic sequencing to identify variations most frequently associated with CNS disease, followed by creation
of mutant viruses to determine the individual impact of identified variations on viral spread between the
simplified neuronal connections of in vitro chamber assays, and the complex neuronal circuits of the murine
retina. The studies outlined in this proposal will provide the first insights into how variations in the neonatal
HSV genome impact neurovirulence and the development of CNS disease.

## Key facts

- **NIH application ID:** 10246399
- **Project number:** 5K08NS109332-05
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Lisa Nowoslawski Akhtar
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,159
- **Award type:** 5
- **Project period:** 2020-05-18 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246399

## Citation

> US National Institutes of Health, RePORTER application 10246399, Neurovirulence determinants of neonatal HSV disease (5K08NS109332-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246399. Licensed CC0.

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