# The role of RNA deletion and duplication events in Powassan virus pathogenesis and evolution

> **NIH NIH R21** · EMORY UNIVERSITY · 2024 · $193,150

## Abstract

Project Summary/Abstract
 RNA viruses frequently undergo recombination, and the resulting deletions and duplications in both
genomic and subgenomic RNA can contribute to the viral lifecycle, pathogenesis, and immune evasion. While
recombination has been studied for some viruses, including mosquito-borne flaviviruses, its role in tick-borne
flaviviruses is unknown. This project will investigate RNA recombination, deletions, and duplications in Powassan
virus, which is an emerging flavivirus that is transmitted by Ixodes scapularis ticks, causes severe encephalitis,
and has been detected in the United States with increasing frequency. The long-term objective of this work is to
understand the biological role of recombination in tick-borne virus infection.
 The goals of the current project are to comprehensively characterize the types, genomic locations, and
host-specific patterns of RNA recombination in Powassan virus. The first Aim is to map recombination junctions,
deletions, and duplications in Powassan virus RNA collected from wild-caught Ixodes scapularis ticks. The
investigators will use laboratory and analysis methods specifically designed for detecting recombination:
ClickSeq for library preparation and ViReMa for analysis. They will sequence samples from an existing biobank
of RNA from over 100 Powassan-positive ticks, representing a range of geography and genetic diversity.
Recombination junctions common to multiple samples are hypothesized to represent biologically meaningful
RNA species, such as structural variants (functional RNA molecules important in the viral lifecycle) or defective
RNAs, dysfunctional RNA molecules that may inhibit wild-type virus replication or modify immune signaling.
Evaluating the role of these RNA species in pathogenesis or transmission will be the focus of future projects.
 The second Aim of the current project is to assess whether there are host-specific patterns in RNA
recombination, as vectorborne viruses must replicate in both arthropod and mammalian hosts throughout their
lifecycle. First, the investigators will use a Powassan virus infectious clone to infect tick and mammalian cell
lines, and carefully measure recombination both intracellularly and extracellularly. They will compare the amount
of recombination, including deletions and duplications, and the specific recombination junctions, between host
cell types. Finally, the investigators will use the infectious clone of Powassan virus to infect mice and nymphal
ticks in order to assess whether observed patterns of recombination are reproducible in vivo.
 Overall, this work will provide critical insight into the currently-understudied role of recombination in
Powassan virus, a representative emerging tick-borne flavivirus. Some recombinant species, such as defective
RNAs, are currently being investigated for therapeutic benefit in other viruses, and thus this project may
ultimately contribute to antiviral treatment of tick-borne flaviviruses. Important...

## Key facts

- **NIH application ID:** 10795083
- **Project number:** 5R21AI176458-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Anne L Piantadosi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $193,150
- **Award type:** 5
- **Project period:** 2023-02-24 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795083

## Citation

> US National Institutes of Health, RePORTER application 10795083, The role of RNA deletion and duplication events in Powassan virus pathogenesis and evolution (5R21AI176458-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10795083. Licensed CC0.

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