Related Experiment Video
Updated: Dec 4, 2025
Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
Powassan Virus Neuropathology and Genomic Diversity in Patients With Fatal Encephalitis
Erica Normandin1,2, Isaac H Solomon3, Siavash Zamirpour1,4
1Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Background:
Powassan virus (POWV) is an emerging cause of severe encephalitis; very little is known about human pathogenicity due to challenges in diagnosis and viral RNA recovery. We present 3 patients with fatal encephalitis due to POWV lineage II (deer tick virus).
Methods:
We obtained 27 unique samples, including from brain biopsy and autopsy, and used metagenomic sequencing, quantitative reverse transcriptase polymerase chain reaction, and a newly developed CRISPR-based diagnostic assay to perform the first detailed characterization of POWV compartmentalization and genomics between and within human subjects.
Results:
In all 3 patients, imaging and histopathology findings were notable for profound cerebellar involvement. All patients were initially diagnosed with POWV by metagenomic sequencing, and 2 of the 3 had negative clinical testing by serology. We detected POWV RNA in 13 clinical samples; levels were highest in the cerebellum, and there was very little involvement of peripheral tissue. We assembled complete POWV genomes from 8 samples, providing unique information about the strains of POWV lineage II (deer tick virus) that infect humans.
Conclusions:
We demonstrate the utility of molecular assays for detecting POWV infection, including in seronegative patients, and nominate viral genomic features that may relate to human infection and neuropathogenicity. The cerebellum was identified as a key target POWV in fatal infection, by radiological and histopathological findings as well as molecular testing.
Insights
Fatal Powassan virus (POWV) encephalitis disproportionately affects the cerebellum. Molecular assays are crucial for diagnosing POWV, even in seronegative patients, revealing key genomic insights into human infection.
Area of Science:
- Neuroscience
- Virology
- Infectious Diseases
Background:
- Powassan virus (POWV) is an emerging pathogen causing severe encephalitis.
- Human pathogenicity and diagnosis are challenging due to difficulties in viral RNA recovery.
- This study examines three fatal encephalitis cases linked to POWV lineage II (deer tick virus).
Purpose of the Study:
- To characterize POWV compartmentalization and genomics within human subjects.
- To investigate the neuropathogenicity of POWV lineage II.
- To evaluate diagnostic methods for POWV infection.
Main Methods:
- Utilized metagenomic sequencing, RT-qPCR, and a novel CRISPR-based assay.
- Analyzed 27 diverse clinical samples, including brain biopsies and autopsy tissues.
- Performed detailed genomic and compartmentalization analyses of POWV.
Main Results:
- Profound cerebellar involvement was observed in all three patients via imaging and histopathology.
- Metagenomic sequencing confirmed POWV in all cases; serology was negative in two.
- POWV RNA was concentrated in the cerebellum, with minimal peripheral tissue involvement.
Conclusions:
- Molecular assays are vital for POWV detection, especially in seronegative individuals.
- Specific viral genomic features may correlate with human infection and neuropathogenicity.
- The cerebellum is a primary target organ in fatal POWV infections.
Related Concept Videos
01:29Subviral Agents
00:36Viral Mutations