# Cellular Requirements for KSHV Latency in Endothelial Cells

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $178,517

## Abstract

Abstract:
KS was one of the first AIDS defining illnesses and world-wide continues to be the most
common tumor of AIDS patients. The main tumor cell of KS is the spindle cell, a cell that
expresses markers of lymphatic endothelium. All spindle cells in late stage tumors maintain
Kaposi's Sarcoma-herpesvirus infection. Kaposi's Sarcoma-herpesvirus (KSHV) is a gamma-
herpesvirus and is the etiologic agent of Kaposi's Sarcoma (KS). Over 95% of spindle cells in the
KS tumor express only latent genes while only a very low percentage express additional lytic
proteins. Current treatments for KS involve general chemotherapy for the tumor but do not
directly target the virus. All direct treatment for herpesviruses target elements of lytic
replication. There are no treatments for latent herpesvirus infection. Due to the limited gene
expression during latency it is difficult to identify viral therapeutic targets for eliminating latent
infection. However, KSHV dramatically alters the host cell during latent infection. Therefore, it
might be possible to target pathological changes to the host cell during latent infection to
eliminate latently infected cells. We have performed a whole genome Crispr/Cas9 screen in
tert-immortalized endothelial cells to identify genes cellular genes and signaling pathways that
are required for the proliferation or survival of latently infected endothelial cells but not their
uninfected counterparts. Our initial studies have identified a large number of cellular genes
required for latently infected cells to proliferate and survive that appear to have little effect on
uninfected endothelial cells. We propose to further validate these studies in primary endothelial
cells. We will also examine specific pathways that were identified in the screen including the
Rho family Guanine exchange factors (GEFs) and GTPase activating proteins (GAPs) and their
signaling pathways. The goals of the proposal are to identify novel cellular targets that could be
used to eliminate cells latently infected with KSHV.

## Key facts

- **NIH application ID:** 9980822
- **Project number:** 5R21CA240479-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Michael Lagunoff
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,517
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980822

## Citation

> US National Institutes of Health, RePORTER application 9980822, Cellular Requirements for KSHV Latency in Endothelial Cells (5R21CA240479-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9980822. Licensed CC0.

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