# "Project 2" Epstein-Barr virus LMP2 IncRNAs

> **NIH NIH P01** · UNIVERSITY OF FLORIDA · 2020 · $282,729

## Abstract

Summary
Epstein-Barr Virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are the leading cause of cancer
in HIV-infected individuals and recent epidemiologic data suggests that these cancers are occurring in increased
frequency in patients treated with combination antiretroviral treatment (cART). The underlying rationale of this
program is that viral and host long noncoding RNAs play a role in gamma-herpesvirus pathogenesis and
tuomorigenesis.
Recent investigations into the function of human lncRNA have begun to illustrate how central this class of RNAs
is to an array of cell regulatory processes such as gene silencing, transcriptional activation, gene imprinting,
RNA maturation, splicing, etc. Based on our recent EBV transcriptomics work, we believe that there are likely
scores of novel viral lncRNAs (vlncRNAs) expressed in different stages of the EBV infection cycle. Collaborative
efforts with the Renne and Tibbetts labs to globally identify and resolve viral transcript structures are similarly
uncovering dozens of novel non-coding KSHV and MHV68 RNAs revealing common themes such as vlncRNAs
that can act as microRNA sponges and latency gene antisense transcripts that potentially contribute to the
regulation of latency and reactivation, two steps that are crucial for virus biology and pathogenesis. In Project
2, we will investigate the functions of three distinct vlncRNA types expressed from the oncogenic latency
membrane protein LMP2 locus, the protein product of which is required for growth transformation of primary
human B cells. One of these vlncRNAs is antisense to LMP2 and is an apparent counterpart of the KSHV LAMP
antisense transcript being investigated in Project 1. We will also investigate a series of unique sense oriented
LMP2 isoforms. This includes chimeric LMP2 transcripts harboring exons from the transforming latency vlncRNA,
RPMS1 (a BamHI A Rightward Transcript (BART) isoform), as well as a circular form of LMP2. We hypothesize
that these LMP2 transcripts have diverse functions ranging from chromatin remodeling to interactions with B-cell
receptor signaling pathways in both reactivation and possibly de novo infection and growth transformation.
Importantly, Project 2 will exploit EBV's ability to growth transform B-lymphocytes to directly address the roles
of both vlncRNAs and EBV regulated cellular lncRNAs in B-cell activation and in HIV-associated lymphomas,
complementing similar investigations being pursued in Projects 1 and 3.

## Key facts

- **NIH application ID:** 9869864
- **Project number:** 5P01CA214091-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** ERIK K FLEMINGTON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $282,729
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869864

## Citation

> US National Institutes of Health, RePORTER application 9869864, "Project 2" Epstein-Barr virus LMP2 IncRNAs (5P01CA214091-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9869864. Licensed CC0.

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