# Epitranscriptomic Regulation of Alphavirus Replication and Transmission

> **NIH NIH R21** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $191,145

## Abstract

Summary
Alphaviruses represent a continuingly emerging challenge to global public health. This is exemplified by the
spread of chikungunya virus from Africa through southern Asia and into the Americas. Additionally, this past
summer has seen an increase in the number of eastern equine encephalitis virus infections and deaths in the
United States. A deeper understanding of the determinants of efficient transmission and replication is needed
to identify targets for transmission interventions. In recent years it has become apparent that modification of
viral RNA impacts it’s function, and the outcome of infection. The proposed research extends on published and
preliminary observations that implicate a particular epitranscriptomic modification of the viral genomic RNA in
the determination of transmission efficiency. This proposal investigates the novel hypothesis that host species
specific modification of the packaged viral genomic RNA impacts the ability of the particle to establish infection
in the next host cell, a prospect of significant consequence for alphaviruses that obligatorily cycle between
mosquito and vertebrate hosts. To examine this the proposed research will: (i) employ multiple sequencing
technologies to determine the methylation state of cytosine residues in the genome of particles produced in
vertebrate and mosquito cells; (ii) examine the biological consequence of disrupting the methylation of the viral
genome through altering the methyltransferase and/or mutating residues found to be frequently modified. The
results of this work will elucidate the pro- and anti-viral effects of cytosine methylation of viral RNA, and lay the
ground work for further investigation of host-specific epitranscriptomic modifications and their role in virus
replication and transmission.

## Key facts

- **NIH application ID:** 10040109
- **Project number:** 1R21AI153785-01
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** RICHARD W HARDY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,145
- **Award type:** 1
- **Project period:** 2020-06-03 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040109

## Citation

> US National Institutes of Health, RePORTER application 10040109, Epitranscriptomic Regulation of Alphavirus Replication and Transmission (1R21AI153785-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10040109. Licensed CC0.

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