TY - JOUR
T1 - Double-stranded RNA immunohistochemistry as a screening tool for viral encephalitis
AU - Piantadosi, Anne
AU - Shariatzadeh, Nima
AU - Bombin, Andrei
AU - Arkun, Knarik
AU - Alexandrescu, Sanda
AU - Kleinschmidt-Demasters, B. K.
AU - Solomon, Isaac H.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Objectives: Viral infections of the central nervous system can be challenging to diagnose because of the wide range of causative agents and nonspecific histologic features. We sought to determine whether detection of double-stranded RNA (dsRNA), produced during active RNA and DNA viral infections, could be used to select cases for metagenomic next-generation sequencing (mNGS) from formalin-fixed, paraffin-embedded brain tissue. Methods: Eight commercially available anti-dsRNA antibodies were optimized for immunohistochemistry (IHC) and the top antibody tested in a series of cases with confirmed viral infections (n = 34) and cases with inflammatory brain lesions of unclear etiology (n = 62). Results: Among known positives, anti-dsRNA IHC produced a strong cytoplasmic or nuclear staining pattern for Powassan virus, West Nile virus, rabies virus, JC polyoma virus, and adenovirus while failing to detect Eastern equine encephalitis virus, Jamestown Canyon virus, or any herpesvirus. All the unknown cases were negative by anti-dsRNA IHC, while mNGS detected rare viral reads (0.3-1.3 reads per million total reads) in 2 cases (3%), with only 1 having potential clinical significance. Conclusions: Anti-dsRNA IHC can effectively identify a subset of clinically relevant viral infections but not all. The absence of staining should not exclude cases from mNGS if sufficient clinical and histologic suspicion exists.
AB - Objectives: Viral infections of the central nervous system can be challenging to diagnose because of the wide range of causative agents and nonspecific histologic features. We sought to determine whether detection of double-stranded RNA (dsRNA), produced during active RNA and DNA viral infections, could be used to select cases for metagenomic next-generation sequencing (mNGS) from formalin-fixed, paraffin-embedded brain tissue. Methods: Eight commercially available anti-dsRNA antibodies were optimized for immunohistochemistry (IHC) and the top antibody tested in a series of cases with confirmed viral infections (n = 34) and cases with inflammatory brain lesions of unclear etiology (n = 62). Results: Among known positives, anti-dsRNA IHC produced a strong cytoplasmic or nuclear staining pattern for Powassan virus, West Nile virus, rabies virus, JC polyoma virus, and adenovirus while failing to detect Eastern equine encephalitis virus, Jamestown Canyon virus, or any herpesvirus. All the unknown cases were negative by anti-dsRNA IHC, while mNGS detected rare viral reads (0.3-1.3 reads per million total reads) in 2 cases (3%), with only 1 having potential clinical significance. Conclusions: Anti-dsRNA IHC can effectively identify a subset of clinically relevant viral infections but not all. The absence of staining should not exclude cases from mNGS if sufficient clinical and histologic suspicion exists.
KW - dsRNA
KW - metagenomic sequencing
KW - viral encephalitis
UR - http://www.scopus.com/inward/record.url?scp=85166395817&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85166395817&partnerID=8YFLogxK
U2 - 10.1093/ajcp/aqad039
DO - 10.1093/ajcp/aqad039
M3 - Article
C2 - 37141170
AN - SCOPUS:85166395817
SN - 0002-9173
VL - 160
SP - 210
EP - 219
JO - American Journal of Clinical Pathology
JF - American Journal of Clinical Pathology
IS - 2
ER -