# "Project 3" MHV68 IncRNA/miRNA interaction in latency and lympomagenesis

> **NIH NIH P01** · UNIVERSITY OF FLORIDA · 2021 · $298,359

## Abstract

Project summary
The transforming human gammaherpesviruses EBV and KSHV establish stable latent infections in B cells,
providing a lifelong reservoir of virus that can contribute to the development of malignant disease. Thus, defining
the mechanisms that govern long-term latency is critical for designing rational strategies to prevent disease. In
vivo studies of gammaherpesviruses in humans have been severely limited by the difficulties of working in the
natural host. Murine gammaherpesvirus 68 (MHV68) is related to EBV and KSHV and causes lymphomas and
lymphoproliferative disease in mice, providing a readily manipulable small animal model for mechanistic studies
of the virus/host relationship in vivo. Like EBV and KSHV, MHV68 expresses lncRNAs whose functions during
infection and pathogenesis are largely unknown. As virus-encoded lncRNAs are abundantly expressed in vivo
in B cells during long-term latency and in hyperplastic B cell lesions during lymphoproliferative disease, we
hypothesize that these lncRNAs play key roles in latency and lymphomagenesis. In support of this, our new data
demonstrates that the MHV68 TMER4 transcript acts a unique lncRNA that is essential for latency and
pathogenesis. Using a combination of cutting-edge high throughput sequencing approaches and a novel
bioinformatic pipeline, we have now generated a comprehensive map of validated MHV68 lncRNA transcripts.
With results from this discovery phase in hand, we will now test the hypothesis that MHV68 lncRNAs are essential
for latency and tumorigenesis. We will: 1) Determine the roles of high priority MHV68 lncRNAs during in vivo
infection; 2) Define the molecular mechanism by which lncRNA TMER4 facilitates latent infection, and determine
the tripartite regulatory relationship between the novel M3M2 lncRNA, antisense TMERs/miRNAs and latency
protein M2, and 3) Determine the role of virus and host lncRNAs in lymphomagenesis. The use of new genomic,
bioinformatic and mutagenesis technology, in conjunction with systematic in vivo analyses of MHV68 lncRNA
mutants, provides an extremely powerful means to determine the molecular mechanism by which lncRNAs
contribute to gammaherpesvirus infection and lymphomagenesis in vivo. Further, the unique collaborative nature
of this program project should allow us to define the contribution of common lncRNA-targeted pathways to
latency and tumorigenesis.

## Key facts

- **NIH application ID:** 10145664
- **Project number:** 5P01CA214091-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Scott A. Tibbetts
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $298,359
- **Award type:** 5
- **Project period:** 2017-02-09 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145664

## Citation

> US National Institutes of Health, RePORTER application 10145664, "Project 3" MHV68 IncRNA/miRNA interaction in latency and lympomagenesis (5P01CA214091-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145664. Licensed CC0.

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