# Progressive Multifocal Leukoenephalopathy: Endemic Viruses and Lethal Brain Disease

> **NIH NIH R35** · BROWN UNIVERSITY · 2020 · $577,779

## Abstract

Program Summary
Progressive Multifocal Leukoencephalopathy (PML) is a major life threatening complication in patients
with AIDS and in patients undergoing immunotherapy for autoimmune diseases such as multiple
sclerosis, Crohn's disease, severe plaque psoriasis, systemic lupus erythematosis, hematologic
malignancies, and rheumatoid arthritis. The disease is paradoxically caused by a common human
polyomavirus following the loss of normal immune surveillance of the central nervous system (CNS).
There are several major gaps in our understanding of the basic biology that underpins the
development of PML. First, the anatomical site of virus persistence is not known but kidney, bone
marrow, and brain have all been postulated to be involved. Second, the mechanisms that govern viral
persistence are not well defined but changes in the viral promoter (archetype to PML-type) and
regulation of a viral microRNA are thought to be critical for transition to the lytic phase. Third, the
mechanisms of viral spread to the CNS and within the CNS are not known. Based on our recent work
we hypothesize that free virus as well as virus enclosed in extracellular vesicles spreads from the
kidney to the choroid plexus and meningeal compartments where replication in CPE cells provides the
means for EV mediated invasion of brain parenchyma. Once in the brain extracellular vesicle
mediated spread is likely to play the major role in spreading the infection because macroglia lack the
principle cellular receptors to support infection by free virus. Our vision for the R35 application is to
further our understanding of these basic mechanisms of infectious spread of virus and to use the
information to identify biomarkers that can predict PML early and in easily accessible compartments
well before the virus has a chance to spread to the CNS. The work should also lead to the
development of novel strategies to treat and prevent PML.

## Key facts

- **NIH application ID:** 9986116
- **Project number:** 1R35NS116836-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Walter J Atwood
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $577,779
- **Award type:** 1
- **Project period:** 2020-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986116

## Citation

> US National Institutes of Health, RePORTER application 9986116, Progressive Multifocal Leukoenephalopathy: Endemic Viruses and Lethal Brain Disease (1R35NS116836-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986116. Licensed CC0.

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