# Role of Host Cell Factors in Newborn Herpes Simplex Virus (HSV) Encephalitis

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $328,198

## Abstract

PROJECT SUMMARY
 The newborn brain is uniquely susceptible to a wide range of pathogens compared to the adult, and this
is exemplified following infection with herpes simplex virus type-1 (HSV-1), the most common cause of viral
encephalitis. The majority of newborns infected with HSV-1 will go on to have severe disease, including viral
dissemination and encephalitis, whereas infection in the adult population typically results in asymptomatic
acquisition or benign mucosal infection. HSV encephalitis in the adult remains rare despite a HSV-1
seroprevalence of 50-80% in this population. The significantly different outcomes between adults and
newborns following HSV infection suggest an age-dependent difference in susceptibility to central nervous
system (CNS) disease based on host factors. A relative immaturity of the neonatal immune system is
commonly implicated in their overall increased susceptibility to HSV and other neurotropic viruses, however,
the precise reasons underlying their increased susceptibility to viral encephalitis remain unknown. The
incomplete understanding of pathogenesis in the neonatal population remains as a critical barrier to improving
survival and neurologic outcomes following HSV encephalitis.
 In this proposal, we plan to investigate the innate immune mechanisms in the brain responsible for
differences in susceptibility and severity of HSV disease between the newborn and adult. We will build on our
previously unfunded work to understand the role of the host response in determining viral tropism within the
brain, the contribution of glial cells to HSV-1 infection, and modulation of the blood brain barrier (BBB) by type I
interferon (IFN) signaling in the newborn during infection. HSV-1 and the host antiviral response has been
frequently studied in the context of neuronal infection, however, there is an emerging role for astrocytes and
microglia in the pathogenesis of viral encephalitis. Preliminary data from our lab demonstrates astrocytic
infection in the newborn brain in addition to neurons, and significant differences in the type I IFN response
between the two age groups. We hypothesize that the contribution of astrocytes and microglia to viral
replication and survival following HSV encephalitis is age-dependent. Our proposed studies will demonstrate
the contribution of type I IFN signaling specifically in astrocytes and microglia to HSV pathogenesis, and how
this response changes through different developmental ages. HSV encephalitis often occurs in the context of
disseminated disease in the newborn, and we also plan to investigate the role of type I IFN in modulating the
BBB during infection and its contribution to HSV spread to the brain. Preliminary data from our lab suggests
that type I IFN treatment improves survival and reduces HSV neuroinvasion during disseminated disease. In
this proposal, we will pursue the innate immune mechanisms that underlie BBB modulation in the newborn
brain, and elucidate the potential ...

## Key facts

- **NIH application ID:** 10133167
- **Project number:** 5R01NS110631-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Richard M Longnecker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,198
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133167

## Citation

> US National Institutes of Health, RePORTER application 10133167, Role of Host Cell Factors in Newborn Herpes Simplex Virus (HSV) Encephalitis (5R01NS110631-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10133167. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*