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Double-stranded RNA immunohistochemistry as a screening tool for viral encephalitis
Anne Piantadosi1, Nima Shariatzadeh1, Andrei Bombin1
1Department of Pathology and Laboratory Medicine and Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, US.
American Journal of Clinical Pathology
|May 4, 2023
Summary
Double-stranded RNA (dsRNA) immunohistochemistry (IHC) can detect some viral central nervous system infections. However, negative dsRNA IHC results should not preclude metagenomic next-generation sequencing (mNGS) if suspicion remains high.
Area of Science:
- Neurology
- Virology
- Pathology
Background:
- Diagnosing viral central nervous system (CNS) infections is difficult due to diverse causative agents and non-specific histological findings.
- Double-stranded RNA (dsRNA) is a byproduct of active RNA and DNA viral replication.
Purpose of the Study:
- To evaluate the utility of anti-dsRNA antibody immunohistochemistry (IHC) for selecting formalin-fixed, paraffin-embedded brain tissue cases for metagenomic next-generation sequencing (mNGS).
- To determine if dsRNA detection can aid in identifying viral CNS infections.
Main Methods:
- Optimized eight anti-dsRNA antibodies for IHC.
- Tested the best antibody on confirmed viral infections (n=34) and inflammatory brain lesions of unknown origin (n=62).
Main Results:
- Anti-dsRNA IHC successfully identified Powassan virus, West Nile virus, rabies virus, JC polyoma virus, and adenovirus.
- The method failed to detect Eastern equine encephalitis virus, Jamestown Canyon virus, and herpesviruses.
- Metagenomic next-generation sequencing (mNGS) detected rare viral reads in 3% of unknown cases, with only one case of potential clinical significance.
Conclusions:
- Anti-dsRNA IHC is effective for a subset of viral CNS infections but not comprehensive.
- A negative dsRNA IHC result should not exclude cases from mNGS if clinical and histological suspicion is present.
