# Identifying susceptibility factors for KSHV infection in human tonsil

> **NIH NIH R01** · CHAPMAN UNIVERSITY · 2020 · $319,647

## Abstract

Abstract/Project Summary
Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic human herpesvirus, which causes Kaposi
sarcoma (KS) as well as B cell lymphoproliferative disorders in the absence of adequate immune control. KSHV-
associated tumors are a significant cause of morbidity and mortality in transplant patients and individuals with
HIV-disease. The oral cavity is an important site for KSHV biology because saliva is believed to be the primary
mode of person-to-person transmission for the virus. The tonsil and other oral lymphoid tissues represent a logical
anatomical site for early infection events because they are in contact with saliva and are rich in target cell types
for KSHV infection including endothelial cells and B lymphocytes. Despite this, the biology of KSHV in the human
tonsil remains poorly understood. We have successfully isolated a variety of primary cell lineages from human
tonsil specimens and have developed robust in vitro infection models for tonsil-derived lymphocytes and non-
lymphocyte cell lines. The current proposal will leverage our library of tonsil lymphocyte specimens and cell lines
in order to explore the fundamental biology of KSHV transmission in this niche. Using ex vivo susceptibility of
tonsil-derived B lymphocytes as a surrogate for overall susceptibility of each tonsil specimen to KSHV infection,
we will use a variety of molecular and cell biology techniques to examine sample-intrinsic factors that may
influence the ability of KSHV to infect a new human host. These factors include: (1) host immunological
parameters (2) host gene expression parameters (3) viral co-infections and (4) bacterial co-infections/microbiome
communities. We will also examine how KSHV manipulates host cytokine signaling during early infection in order
to determine whether cytokines can be manipulated to limit the establishment of KSHV infection in tonsil
lymphocytes. Finally, we will determine how KSHV spreads within and between tonsil-derived cell types and
determine which cell types are (1) important for transferring infection to disease-relevant cell types (2) potential
sources of KSHV shedding into saliva. The results of this research will provide critical information about factors
influencing KSHV transmission, and will highlight novel therapeutic targets that can be exploited to limit the
spread of KSHV within the human population.

## Key facts

- **NIH application ID:** 9893850
- **Project number:** 5R01CA239590-02
- **Recipient organization:** CHAPMAN UNIVERSITY
- **Principal Investigator:** Jennifer E Totonchy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $319,647
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893850

## Citation

> US National Institutes of Health, RePORTER application 9893850, Identifying susceptibility factors for KSHV infection in human tonsil (5R01CA239590-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9893850. Licensed CC0.

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