# Neurotropic Viral Infection in CNS Aging and Alzheimer's Disease COVID-19 Supplement

> **NIH NIH R00** · UNIVERSITY OF NORTH CAROLINA CHARLOTTE · 2020 · $243,918

## Abstract

Project Summary
The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its
resulting disease (COVID-19) emerged as an unprecedented worldwide healthcare crisis. COVID-19 primarily
manifests as a lower respiratory tract infection and viral pneumonia; however, neurotropism is a common
feature of coronaviruses (CoVs) and has been documented for almost all betacoronaviruses, the clade to
which SARS-CoV-2 belongs. It was reported that 36% of COVID-19 patients develop neurologic symptoms,
but whether these are due to CNS infection, systemic inflammatory response, or intensive care unit delirium is
unknown. Advanced age is a significant risk factor for developing severe infection from SARS-CoV-2. Aging is
associated with compromised cellular immunity and blood brain barrier dysfunction, which may increase the
vulnerability of the CNS to infection and long-term damage from systemic infections. Neuroinflammation is
recognized as contributing to disorders of the central nervous system (CNS) including Alzheimer’s disease
(AD). Our overarching hypothesis is that viral encephalitis enhances inflammatory events that accelerate CNS
aging processes and contribute to the development of AD pathology. The original application proposed to use
West Nile virus (WNV) as a model of viral encephalitis to examine behavioral, cellular, and molecular
mechanisms of CNS recovery. Here we propose to enhance this research by investigating a murine CoV
model, mouse hepatitis virus A-59. Like WNV, CoVs are enveloped positive-stranded RNA viruses, but have
distinct effects in the CNS. The addition of this CoV model will augment the original scope of the proposal by
allowing the comparison of results from each of the two models to determine universal aging processes that
result from viral infection. In this supplement, we propose to test the hypothesis that advanced age increases
the risk of lethal neurotropic infection by CoV and that inflammatory processes initiated by infection may
contribute to the pathogenesis of AD. Aim 1 will determine the impact of advanced age on acute viral infection
and antiviral response. Aim 2 will identify the effect of advanced age on microglial response to infection. Aim 3
will investigate the impact of viral encephalitis on pathological Tau accumulation. These studies will address
the urgent need to understand how aging impacts CoV infections, the impact of viral encephalitis on aging
processes in the CNS, and their contribution to neurodegenerative diseases. The experiments proposed here
will be analyzed in parallel with our established model of WNV to enhance the goals of the original proposal.

## Key facts

- **NIH application ID:** 10188852
- **Project number:** 3R00AG053412-04S1
- **Recipient organization:** UNIVERSITY OF NORTH CAROLINA CHARLOTTE
- **Principal Investigator:** Kristen Emily Funk
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,918
- **Award type:** 3
- **Project period:** 2019-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188852

## Citation

> US National Institutes of Health, RePORTER application 10188852, Neurotropic Viral Infection in CNS Aging and Alzheimer's Disease COVID-19 Supplement (3R00AG053412-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10188852. Licensed CC0.

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