# Identification of host factors required by the tick-borne Powassan virus

> **NIH NIH R21** · ROCKEFELLER UNIVERSITY · 2021 · $254,250

## Abstract

PROJECT SUMMARY
Flaviviruses cause significant morbidity and mortality worldwide. The sudden emergence and spread of viruses
such as Zika illustrate our vulnerability and emphasize the need for preparedness against related emerging
viruses. In addition to mosquito-borne flaviviruses, members of tick-borne flaviviruses pose an increasing global
threat for which we lack effective antivirals.
Powassan virus (POWV) is an emerging virus transmitted by the bite of infected Ixodes ticks. The
seroprevalence of POWV in humans is mostly unknown as infections may often be asymptomatic. However,
symptomatic POWV infections may progress in to severe and sometimes fatal encephalic disease with mortality
rates of ~10% and surviving patients often suffer from debilitating long-term neurologic symptoms. The severe
clinical consequences of infections with POWV and other tick-borne flaviviruses and the lack of specific
treatments highlight an urgent need for a better understanding of these viruses in their tick and mammalian hosts
so that preventative and therapeutic treatments can be developed.
 The goal of this project is to identify host factors required by POWV that may also impact a wide range
of existing and emerging flaviviruses. These host proteins may represent suitable targets for antiviral
interventions, and we hypothesize that impaired virus replication due to their inhibition may allow innate and
adaptive immunity to control the infection. Further, we propose to compare a panel of flaviviruses, including
POWV, and their requirements for the identified host factors in both vertebrate and invertebrate cells. We believe
these approaches will allow us to prioritize candidate genes for future drug development studies.
 The proposed studies will utilize CRISPR/Cas9 screening technology to knock out every gene in the
human genome with the goal of identifying host factors that facilitate POWV infection. We will use a similar
approach in a targeted, arrayed format to evaluate the identified host factors in various human and tick cell lines
during infection with diverse flaviviruses.
 We expect that this work will broaden our understanding of tick- and mosquito-borne flaviviruses,
specifically in terms of clinical phenotype (encephalitic vs hemorrhagic disease) and the shared need for host
factors. In addition, it will help to define which genes govern host species and tissue tropism. Together, this work
will provide a wealth of new insights into many aspects of flavivirus biology.

## Key facts

- **NIH application ID:** 10154884
- **Project number:** 1R21AI153927-01A1
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Charles M Rice
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2020-11-23 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154884

## Citation

> US National Institutes of Health, RePORTER application 10154884, Identification of host factors required by the tick-borne Powassan virus (1R21AI153927-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10154884. Licensed CC0.

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