# Effects of HSV-1 infection on neural progenitor cell biology in vitro and in vivo

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $392,009

## Abstract

8. Abstract
We will investigate Herpes simplex virus type 1 (HSV-1) infection of neural progenitor cells (NPCs)
in our R01 application. In immunocompetent individuals, HSV-1 infection is the most common
cause of encephalitis (HSE). Although antiviral therapy has improved its prognosis, the majority
of HSV-1 encephalitis survivors suffer from permanent neurological sequelae. The chronic lesions
in HSE patients have been observed in regions associated with memory formation, which include
the hippocampus and associated limbic structures. The severity of sequela in HSE is related to
the severity of damage to these regions.
HSV-1 displays tropism for hippocampus (subgranular zone, SGZ) and the subventricular zone
(SVZ) of the lateral ventricles. Both regions are rich in NPCs, which differentiate into neurons and
glial cells. These regions are thus major niche areas for adult neurogenesis. Despite the pivotal
role played by the NPCs in adult neurogenesis, the effect of HSV-1 on NPCs proliferation,
differentiation and migration is largely unknown. Furthermore, whether NPCs may represent
reservoirs of HSV-1 in the CNS is unknown.
Here, we aim to model the interaction of HSV-1 with NPCs using three-dimensional (3D) cultures
of human CNS cells derived from induced pluripotent stem cells (hiPSCs); we will also build on a
mouse model of encephalitis to enable experiments not feasible in human cells in vitro.
In Aim 1, we will investigate early-stage effects of HSV-1 infection on proliferation, differentiation,
and migration of NPCs derived from hiPSCs in three-dimensional (3D) culture systems that we
have designed; the model incorporates NPCs and their derivatives. In Aim 2, we will employ a
mouse model of encephalitis to investigate the distribution of HSV-1 in the hippocampus and SVZ,
the effects of HSV-1 infection on NPCs proliferation and analyze NPCs in surviving mice for
periods ranging from 6 months to 1 year. Also, we will determine if there is evidence of HSV-1
latency and reactivation in NPCs. In Aim 3, we will investigate: i) HSV-1 latency in NPCs; ii) the
effect of HSV-1 infection on pathways regulating the differentiation fate of NPCs pathways
regulating; and iii) the consequences of persistent infection on NPCs function. The rodent and the
iPSC data will be synthesized. We hypothesize that i) HSV-1 impairs NPC processes required
for neurogenesis; ii) HSV-1 can establish latency in NPCs.
What is learned from this project will improve our understanding of HSV-1 encephalitis. We
possess the relevant expertise for the proposed work.

## Key facts

- **NIH application ID:** 10201788
- **Project number:** 5R01NS115082-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** David C. Bloom
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,009
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201788

## Citation

> US National Institutes of Health, RePORTER application 10201788, Effects of HSV-1 infection on neural progenitor cell biology in vitro and in vivo (5R01NS115082-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201788. Licensed CC0.

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