# Theiler's virus RNA in exosomes secreted by infected microglia

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2021 · $232,000

## Abstract

PROJECT SUMMARY
Theiler’s murine encephalomyelitis virus (TMEV) infection of susceptible mice leads to the establishment of a
persistent virus infection the central nervous system (CNS). The persistent TMEV infection is associated with
an inflammatory response that leads to the development of a chronic, progressive demyelinating disease.
TMEV remains persistent in microglia cells which are the CNS resident immune cell population. We have
previously shown that TMEV- infected microglia become activated to secrete pro-inflammatory cytokines,
chemokines, and effector molecules. TMEV-induced demyelinating disease serves as a mouse model for
multiple sclerosis (MS) in humans which is a demyelinating disease of the CNS associated with an
inflammatory immune response. Activated microglia have been identified in both early and late demyelinating
lesions in MS patients, and thus have been suggested to play a role in the inflammatory immune response.
The causative agent for MS has not been determined, however epidemiological studies have suggested that a
virus infection during childhood may begin the disease process where clinical signs of disease do not appear
until adulthood. The proposed mechanism by which virus infections may trigger demyelinating disease is
through bystander damage and bystander activation. Recently we have determined that TMEV- infected
microglia secrete exosomes. Exosomes are microvesicles released by cells that are taken up by other cells
and thus represent a means of cell to cell communication. Exosomes package mRNA, miRNA, DNA, and
proteins from the cytoplasm of the cell which are then transferred to the cytoplasm of the recipient cell. We
have recently determined that exosomes secreted by microglia during TMEV infection contain viral RNA, thus
we propose that exosomes may contribute to persistent virus infection via transfer of viral RNA to bystander
cells. We further propose that the viral RNA in exosomes secreted by microglia during TMEV infection activate
bystander CNS cells to promote the inflammatory response associated with development and progression of
demyelinating disease. We will first determine whether the viral RNA in exosomes secreted by virus infected
microglia are transferred to uninfected cells and replicate to maintain virus infection. We will further determine
whether the viral RNA in exosomes secreted by microglia during TMEV infection activate bystander CNS cells,
such as microglia, astrocytes, and neurons, via innate immune receptors to express pro-inflammatory
cytokines, chemokines, and effector molecules. Most importantly, we will determine whether viral RNA in
exosomes secreted by microglia during persistent TMEV infection can maintain viral persistence and activate
an inflammatory immune response that promotes development and progression of demyelinating disease in
naïve mice. These studies may provide a new mechanism by which viral RNA in exosomes secreted by
microglia may be mediating disease pathogene...

## Key facts

- **NIH application ID:** 10126808
- **Project number:** 5R21AI151595-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** JULIE K OLSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $232,000
- **Award type:** 5
- **Project period:** 2020-03-12 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126808

## Citation

> US National Institutes of Health, RePORTER application 10126808, Theiler's virus RNA in exosomes secreted by infected microglia (5R21AI151595-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10126808. Licensed CC0.

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