# EV-D68-induced CNS disease: pathogenic mechanisms and identification of therapeutic targets.

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $340,156

## Abstract

Virus infections of the central nervous system (CNS) are a significant cause of morbidity and mortality
worldwide. Proven treatments are limited to only a few viruses and even when treatments exist (e.g. acyclovir
for herpes simplex encephalitis) disability and death remain significant. Our knowledge of viral CNS infections,
particularly those involving the spinal cord, is limited and serves as a barrier against the development of novel
treatments for these devastating diseases. Enteroviruses are an important cause of virus-induced CNS
infections. Although poliovirus (PV), is perhaps the most well-known of the neurotrophic enteroviruses, several
non-polio human EVs also target the CNS and are responsible for numerous clinical manifestations, including
encephalitis, myelitis and meningitis. Non-polio EVs are common, causing an estimated 10–15 million or more
symptomatic annual infections in the US alone. Though most of these infections do not result in CNS disease
data from ourselves and others suggest that these viruses can acquire the ability to be neurovirulent. In recent
years large outbreaks of enteroviruses have occurred worldwide and neurotropic enteroviruses have been
deemed “re-emerging pathogens”. In 2014, the United States experienced an epidemic of acute flaccid myelitis
(AFM) cases in children during a nationwide outbreak of previously rare enterovirus D68 (EV-D68) respiratory
disease. Approximately 50% of AFM patients had EV-D68 detected by RT-PCR in respiratory secretions,
although EV-D68 was not detected in cerebrospinal fluid from any patient, preventing the establishment of a
causative link between EV-D68 and AFM. We have recently shown that clinical isolates of EV-D68 from the
2014 outbreak cause neurologic disease in neonatal mice and propose to use this novel model of virus-induced
CNS disease to; (i) increase our understanding of EV-D68-induced CNS disease and investigate how viruses
evolve to become neurovirulent; (ii) delineate pathogenic mechanisms that are triggered in the CNS following
EV-D68 infection; and (iii) evaluate potential therapeutic targets for EV-D68 induced CNS disease. Our
experience with other animal models of virus-induced CNS disease will allow us to rapidly identify whether
mechanisms involved in EV-D68 pathogenesis are common to other viruses that infect the CNS and whether
treatments which are effective against EV-D68-induced CNS disease have broad spectrum applicability to other
virus-induced CNS diseases. Our results may also have relevance non-viral causes of CNS disease, including
neurodegeneration

## Key facts

- **NIH application ID:** 10225583
- **Project number:** 5R01NS101208-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kenneth L. Tyler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $340,156
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225583

## Citation

> US National Institutes of Health, RePORTER application 10225583, EV-D68-induced CNS disease: pathogenic mechanisms and identification of therapeutic targets. (5R01NS101208-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10225583. Licensed CC0.

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