# KSHV immortalization of human lymphatic endothelial cells

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $382,049

## Abstract

Abstract:
Opportunistic infections are a major cause of morbidity and mortality of AIDS patients in developing
countries and AIDS patients are susceptible to a number of cancers caused by opportunistic infections.
Kaposi's Sarcoma (KS) is the most common tumor of AIDS patients and is the most commonly reported
tumor overall in parts of Africa. The etiologic agent of KS is Kaposi's Sarcoma-associated herpesvirus
(KSHV or HHV-8). KSHV is invariably found in the main KS tumor cell, the spindle cell, a cell of
endothelial origin, where the virus is present predominantly in the latent state. Spindle cells express
markers of lymphatic endothelial cells and appear to be most closely aligned with this endothelial cells
type. While KSHV is clearly an oncogenic virus, little is known about the early steps of how KSHV
infection of endothelial cells leads to tumors. It is generally recognized that one of the early steps of
tumor formation is immortalization of cells. There are two main steps in immortalization of human cells,
senescence and crisis. While there have been studies that have examined KSHV Induced immortalization
and transformation, no clear tractable and reliable relevant human cell system has be identified. We
recently found that KSHV infection of primary neonatal lymphatic endothelial cells leads to bypass of
senescence, the first step in immortalization. This proposal will further analyze the KSHV mediated
bypass of senescence and determine if KSHV can drive full immortalization or if other genetic steps are
necessary. Both the cellular and viral mechanism of KSHV mediated immortalization of lymphatic
endothelial cells will also be elucidated. These studies provide a robust system for analyzing KSHV
mediated immortalization of the cell type most closely related to the main KS tumor cell, the spindle cell.
A deeper understanding of how KSHV induces the earliest steps in immortalization will help identify how
KSHV alters endothelial cells to become spindle cells and ultimately KS tumors and potentially provides
novel therapeutic avenues for KS cell proliferation.

## Key facts

- **NIH application ID:** 9850524
- **Project number:** 5R01CA217788-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Michael Lagunoff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,049
- **Award type:** 5
- **Project period:** 2018-02-12 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850524

## Citation

> US National Institutes of Health, RePORTER application 9850524, KSHV immortalization of human lymphatic endothelial cells (5R01CA217788-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9850524. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*