# "Project 1" KSHV-encoded Inc RNAs and alteration of host IncRNA expression

> **NIH NIH P01** · UNIVERSITY OF FLORIDA · 2020 · $281,327

## 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
targetome, we identified several hundred host cellular lncRNAs as putative miRNA targets.
Furthermore, infection of endothelial cells with wtKSHV induced dramatic dys-regulation of host
lncRNAs including the down-regulation of 533 lncRNAs. Of these 126 were rescued when cells
were infected with a KSHV recombinant that lacked 10 of 12 KSHV miRNAs. Together these
data strongly suggest that both KSHV encoded proteins and miRNAs contribute to dysregulation
of host lncRNAs. Importantly, ten lncRNAs that are perturbed following KSHV infection,
including HOTTIP, ANRIL, Meg3, and UCA1 are reported to be associated with human cancers.
We demonstrate that up-regulation of UCA1 affects proliferation and migration of KSHV infected
endothelial cells. Additionally, we provide experimental evidence that the anti-sense LANA
transcript is bound by EZH2/PRC2 complexes and may contribute to the regulation of viral
latency. These data suggest that viral lncRNAs are important regulators of viral gene expression
and hence may be important for viral pathogenesis and/or tumorigenesis. To understand the
role of lncRNAs in viral biology we propose to functionally study viral lncRNAs and to determine
underlying mechanisms and phenotypical consequences of host lncRNA dysregulation in KS
pathogenesis. Importantly, experimental findings observed in appropriate tissue culture models
of lymphoid and endothelial origin, will be validated using clinical specimens from AIDS
malignancies in collaboration with Dr. Chris Parsons. Moreover, this project will be performed in
close collaboration with Projects 2 (EBV) and 3 (MHV68), with the goal of identifying pathways
that are commonly regulated by cancer-associated gamma-herpesvirus lncRNAs. Identifying
such common regulatory pathways may point to novel virus-specific therapeutic strategies. We
note that to date several miRNA and lncRNA based therapeutics are in different stages of
clinical development.

## Key facts

- **NIH application ID:** 9869863
- **Project number:** 5P01CA214091-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** ROLF F RENNE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $281,327
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869863

## Citation

> US National Institutes of Health, RePORTER application 9869863, "Project 1" KSHV-encoded Inc RNAs and alteration of host IncRNA expression (5P01CA214091-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9869863. Licensed CC0.

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