# "Project 1" KSHV short and long noncoding RNAs and alteration of host IncRNA expression

> **NIH NIH P01** · UNIVERSITY OF FLORIDA · 2024 · $77,664

## Abstract

PROJECT SUMMARY
Kaposi's sarcoma-associated herpesvirus (KSHV), a human gamma-herpesvirus, is the causative agent of AIDS 
malignancies like KS and primary effusion lymphomas (PEL). In recent years it became clear that pathogenic 
herpesviruses including EBV, KSHV, and MHV68 express numerous long non-coding RNAs (lncRNAs) many of 
which are in antisense orientation to protein coding transcripts. The function and structure of these RNAs is 
largely unknown. In addition, these viruses express microRNAs (miRNAs). While characterizing the KSHV 
miRNA targetomes using a modified Crosslinking and Sequencing of Hybrids (qCLASH) protocol, we identified 
several hundred host cellular lncRNAs as putative miRNA targets. These data strongly suggest that both KSHV 
encoded proteins and miRNAs contribute to dysregulation of host lncRNAs. Importantly, 34 lncRNAs that are 
perturbed following KSHV infection, including MALAT1, HOTTIP, ANRIL, Meg3, UCA1 and GAS-5 are reported 
to be associated with human cancers. We also linked both mRNA and lncRNA targets to cancer hallmark 
phenotypes such as proliferation, migration, angiogenesis, and glucose metabolism, and started to identify 
signaling pathways that are perturbed by KSHV miRNAs in human endothelial cells as a model for KS. We also 
identified aberrant splicing as an additional cancer hallmark phenotype. Here we propose to extend our studies 
by integrating multi-omics data sets from qCLASH, RNAseq and miRNAseq data to comprehensively analyze 
miRNA-regulated gene regulatory networks in KSHV infected endothelial cells. Moreover, we propose to validate 
our findings in a significant number of human tumor samples and by generating the first KS tumor miRNA 
targetome by qCLASH. These studies will be performed in a comparative fashion with Projects 2 and 3 and 
furthermore will be supported by Cores B, C, and D. In addition, we are functionally studying the role of the 
antisense LANA transcript (ALT) for which we have identified 81 putative binding proteins using a highly 
innovative RNA-pulldown assay. Moreover, we will study the role of a newly identified class of viral circular RNAs 
that has been discovered by this program. In summary, the goal of this project is to delineate the role of viral 
lncRNAs and host cellular lncRNAs that are perturbed by viral infection in AIDS malignancies.

## Key facts

- **NIH application ID:** 11140081
- **Project number:** 3P01CA214091-08S1
- **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:** $77,664
- **Award type:** 3
- **Project period:** 2017-02-09 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11140081

## Citation

> US National Institutes of Health, RePORTER application 11140081, "Project 1" KSHV short and long noncoding RNAs and alteration of host IncRNA expression (3P01CA214091-08S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11140081. Licensed CC0.

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