# Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies

> **NIH NIH P01** · UNIVERSITY OF FLORIDA · 2024 · $76,753

## Abstract

SUMMARY
The goal of this program is to use comparative analysis of KSHV, EBV and MHV68 short and long noncoding
RNAs to reveal conserved functions of, and regulatory nodes targeted by, γ-herpesvirus noncoding RNAs during
tumorigenesis. Our unifying hypothesis is that A) γ-herpesviruses utilize short and long noncoding RNAs to
regulate both virus and host gene expression, and B) viral noncoding RNAs and/or virus-perturbed host lncRNAs
directly contribute to the genesis of HIV-associated malignancies. In support of this hypothesis, our program has
made a number of seminal findings during the first funding period, including: identification of high confidence
miRNA targetomes across all three viruses; demonstration of host lncRNA de-regulation in γ-herpesvirus infected
cells; discovery of circRNAs across all three viruses; global resolution of EBV and MHV68 transcriptomes and
discovery of new noncoding transcripts; demonstration that noncoding RNAs are the predominant viral gene
products detectable in some EBV+ malignancies; and demonstration of the first in vivo function for the long-
studied EBV EBER1 noncoding RNA. To date, our results from the first cycle have been reported in 20 research
publications and 5 review articles. To continue to address our unifying hypothesis we propose three highly
integrated projects: Project 1, led by Dr. Renne (University of Florida, UF), will mechanistically study viral
lncRNAs and how KSHV-encoded miRNAs induce alterations of host lncRNA expression in the context of HIV-
associated KSHV malignancies. Project 2, led by Dr. Flemington (Tulane University) will interrogate the role of
EBV (and KSHV) miRNA cluster inhibition of host miRNA maturation through “microprocessor overload” in the
context of HIV-associated EBV malignancies. Project 3 led by Dr. Tibbetts (UF) will investigate the function of
MHV68 miRNAs and short noncoding RNAs and EBV EBERs in a facile murine chronic infection and
tumorigenesis system. The well-organized Administrative core (Core A, Leader: Rolf Renne) will continue to
maintain oversight and organization of the program, including biostatistical consultation and adherence to rigor,
reproducibility, and transparency standards. Three service cores support all three projects: The RNA-seq and
Bioinformatics Core (Core B, Leader: Erik Flemington) at Tulane University will continue to have high impact by
developing innovative algorithms and data analyses pipelines. The Recombinant Virus Core (Core C, Leader:
Rolf Renne) at UF, which has supported the generation and quality control of more than 60 recombinant viruses,
will continue to innovate by implementing CRISPR-Cas-based techniques. The Clinical Sample and
Tumorigenesis Core (Core D, Leader: Scott Tibbetts) at UF will support the analysis of a significant numbers of
EBV and KSHV-associated tumor samples and perform all proposed tumorigenesis studies. In summary, this
program project, which has already had sustained impact on the field, will fur...

## Key facts

- **NIH application ID:** 10977258
- **Project number:** 3P01CA214091-08S2
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** ROLF F RENNE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,753
- **Award type:** 3
- **Project period:** 2017-02-09 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977258

## Citation

> US National Institutes of Health, RePORTER application 10977258, Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies (3P01CA214091-08S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10977258. Licensed CC0.

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