# Elucidating the function of a family of respiratory viral long noncoding RNAs

> **NIH NIH R21** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $228,535

## Abstract

PROJECT SUMMARY
Understanding the functions and targets of viral noncoding RNAs (ncRNAs) may provide valuable insight into
host antiviral defenses and seed new therapies. However, determining the function of longer ncRNAs is still an
emerging discipline with no clear formula for success. There is an urgent need to fill in this gap in knowledge
because doing so opens up new avenues for understanding virus infection and RNA biology, and may yield
information on effective treatment options for virus-associated disease. We have discovered a family of long
non-protein-coding RNAs (lncRNAs) shared amongst three diverse human respiratory viral pathogen families,
of which the Adenovirus (AdV) virus-associated RNAs (VA RNAs) serve as the founding and prototypic members.
Our long-term goal is to define the mechanisms by which ncRNA is associated with infectious and immunological
disease. Consistent with this goal, our overall objective in this R21 proposal is to determine the function of a
family of viral lncRNAs shared amongst different pathogenic members of the Adeno-, Polyoma, and Parvo- virus
families. Our central hypothesis is that members of the family of VA-like (VA-L) ncRNAs each share structural
features to inactivate common host targets including PKR and the related kinase GCN2, thereby blocking host
defenses and promoting virus infection. Our hypothesis is supported by strong preliminary data demonstrating
that engineering chimeric viruses to express any of the VA-L RNAs rescues defects in replication associated
with mutant viruses lacking VA-L RNA expression. The rationale for this proposed research is that, once it is
known how VA-L RNAs act to promote virus infection, new insights relevant to respiratory viral disease and
treatments will be gained, while providing a template for future studies aimed at identifying the function of the
increasing number of known viral ncRNAs. We plan to test our central hypothesis and complete the objectives
outlined in this proposal via the following two specific aims: 1. Determine the relative activities and essential
features of the VA-L RNAs in promoting virus infection. 2. Determine VA-L RNA host targets and their mechanism
of inactivation. We expect the outcomes of these proposed experiments will provide a blueprint for future work
on identifying targets of viral ncRNAs. Additionally, we expect the results from this proposed work to have an
immediate impact because they will likely identify GCN2 as a previously unappreciated antiviral factor triggered
by amino acid depletion that is associated with virus infection, making manipulation of GCN2 a candidate for
increased production of viral vectors and/or new classes of pan-viral therapeutics. This contribution will be
significant because it is expected to be of potential translational importance in the prevention of virus-associated
respiratory diseases while also solving a long-standing mystery in the AdV and ncRNA fields. The research
proposed in this app...

## Key facts

- **NIH application ID:** 9931155
- **Project number:** 5R21AI147178-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Christopher S. Sullivan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,535
- **Award type:** 5
- **Project period:** 2019-05-17 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931155

## Citation

> US National Institutes of Health, RePORTER application 9931155, Elucidating the function of a family of respiratory viral long noncoding RNAs (5R21AI147178-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9931155. Licensed CC0.

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