# Messenger RNA capping and methylation in pneumoviruses

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $469,725

## Abstract

Abstract
This application is to renew a grant to study RNA methylation in pneumoviruses. Pneumoviridae is a new virus
family, created in 2016 by elevating the paramyxoviral subfamily Pneumovirinae to family status. The
Pneumoviridae family includes two medically important pathogens, human respiratory syncytial virus (RSV) and
human metapneumovirus (hMPV), which are the leading causative agents of acute viral respiratory tract
infections in infants, young children, the elderly, and immunocompromised individuals. Despite the enormous
economic loss and emotional burden these viruses cause, no vaccines or anti-viral drugs are currently available.
Development of such agents requires a better understanding of all aspects of their life cycle. In the last grant
period, we have revealed the unique mechanism of mRNA capping and cap methylation in pneumoviruses. We
recently discovered that pneumovirus genome, antigenome, and mRNAs are also methylated at internal
adenosine residues to form N6-methyladenosine (m6A) by host m6A methyltransferase complex. Although m6A
methylation has been discovered in viral RNA in early 1970s, the biological function of m6A in the virus life cycle,
pathogenesis, and immunity has been a mystery for four decades. We have found that the internal m6A
methylation in viral RNAs promotes pneumovirus replication and gene expression. The objectives of the current
application are to determine the roles of internal m6A methylation in pneumovirus replication and pathogenesis
in vivo; and to define mechanism(s) by which m6A methylation modulate pneumovirus life cycle. Our Specific
Aims are: (1) to define the host m6A machinery that regulates pneumovirus replication and gene expression; (2)
to define the mechanism(s) by which internal m6A promote pneumovirus replication and gene expression; and
(3) to define the roles of m6A methylation in pneumovirus replication and pathogenesis in a cotton rat model. The
successful completion of this work will not only advance our understanding of m6A methylation in regulating
pneumovirus life cycle and pathogenesis, but also provide a novel approach for developing live attenuated
vaccine candidates and antiviral drugs by inhibiting viral m6A methylation.

## Key facts

- **NIH application ID:** 9857527
- **Project number:** 5R01AI090060-07
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jianrong Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $469,725
- **Award type:** 5
- **Project period:** 2010-12-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857527

## Citation

> US National Institutes of Health, RePORTER application 9857527, Messenger RNA capping and methylation in pneumoviruses (5R01AI090060-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857527. Licensed CC0.

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