# Developing a robust platform to identify unexpected and novel viruses in human brain tissue

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $480,375

## Abstract

Project Summary / Abstract
 Central nervous system infections with RNA viruses cause severe neurological deficits and death, and
are extremely challenging to diagnose. This multiple PI proposal presents an innovative research program that
will provide the foundation for a comprehensive viral diagnostics pipeline to rapidly diagnose RNA virus
infections from surgical brain biopsies. The investigators will combine two cutting-edge techniques for viral
detection, screening with double-stranded RNA immunohistochemistry (dsRNA IHC) to identify cases with a
high likelihood of a viral etiology, and unbiased metagenomic next-generation sequencing (mNGS) for specific
virus identification and genome analysis.
 To develop the dsRNA IHC screening assay, six commercially available anti-dsRNA antibodies will be
optimized in formalin-fixed, paraffin-embedded (FFPE) brain tissue and evaluated in a series of known
infectious and non-infectious cases. The top candidates will be tested in a set of brain biopsies with
inflammation of unclear etiology and compared to results of mNGS performed in parallel. The development of
this assay will facilitate efficient screening of FFPE tissue samples from patients with neurological disease of
unclear pathogenesis to identify those with a high likelihood of viral etiology. To improve mNGS methods for
FFPE brain tissue, new laboratory techniques will be tested to increase the yield and quality of viral RNA
extracted. In addition to virus identification, mNGS will be used to perform full-genome deep sequencing of
viruses. These results can be applied to molecular epidemiology, disease surveillance, and understanding
pathogen-host interactions. Overall, this project will enhance our understanding of RNA viruses that cause
CNS infection, inform future studies of virus evolution and pathogenesis, and lay the foundation for the
development of a comprehensive viral diagnostics pipeline that will substantially improve the care of patients
with devastating CNS infections. This work aligns very well with the NINDS mission to seek and apply
fundamental knowledge of the brain to reduce the burden of neurological disease.
 This R21 Exploratory Neuroscience Research Grant proposal will support and expand the collaboration
between the two PIs. The unique combination of expertise in neuropathology, infectious disease pathology,
virology, clinical infectious disease, and metagenomic sequencing demonstrate the requisite skills and
perspective needed to achieve the goals of this proposal. The stimulating environments of Brigham and
Women’s Hospital, Harvard University, and Emory University are extremely well suited to the proposed
research plan, which not only provide critical equipment and facilities infrastructure, but also mentorship, formal
opportunities to present and discuss results, and eventual venues to implement this clinical testing
prospectively.

## Key facts

- **NIH application ID:** 10105533
- **Project number:** 1R21NS119660-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Anne L Piantadosi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $480,375
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105533

## Citation

> US National Institutes of Health, RePORTER application 10105533, Developing a robust platform to identify unexpected and novel viruses in human brain tissue (1R21NS119660-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10105533. Licensed CC0.

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