# Project 3

> **NIH NIH U54** · LSU HEALTH SCIENCES CENTER · 2024 · $301,515

## Abstract

ABSTRACT
Kaposi sarcoma (KS), an HIV/AIDS-associated malignancy, is one of the most prevalent cancers in people
living with HIV-1 (PLWH) in sub-Saharan Africa (SSA). AIDS-associated KS is often aggressive with a high
rate of recurrence despite suppressive antiretroviral therapy and chemo/radiotherapy. Kaposi sarcoma-
associated herpesvirus (KSHV) is the etiologic agent associated with KS. The high prevalence of both KSHV
and HIV-1 put millions of people in SSA at an increased risk of developing KS in their lifetime. Similar to other
herpesviruses, KSHV can remain latent with undetected viral load, but infected individuals can be viremic
periodically, suggesting the presence of an unknown reservoir or reservoirs that are harboring the KSHV
infected or transformed cells and virus emerged after suppressive treatment to lead to KS. Our team has
previously shown that KSHV can be found in brain tissues. The lack of a suitable animal model and the inability
to systematically sample various tissue compartments from KSHV infected individuals have hindered the quest
to locate these KSHV reservoirs in humans. However, with our recently established capability of full-body
autopsies on postmortem donors in SSA, we can now assess the presence or absence of KSHV reservoirs
throughout the entire human body in KSHV infected individuals. Our overall objective is to identify the KSHV
tissue and cellular reservoirs in KSHV seropositive individuals, and to determine the effects of HIV-1 infection
and KS on the size and distribution of these reservoirs. We hypothesize that KSHV reservoirs can be found in
multiple tissue sites, and the size and distribution of the reservoirs will increase in HIV-1 infected individuals
and KS patients. We will accomplish our main objective through the following specific aims: 1) Identify the
KSHV tissue reservoirs and determine the magnitude and breadth of the tissue reservoirs in both
asymptomatic and symptomatic KS with or without HIV co-infection. 2) Identify the KSHV infected cell types
and determine whether HIV-1 infection and symptomatic KS affect the size and distribution of KSHV infected
cell types and latency/lytic expression of the KSHV cellular reservoirs. This proposed study is significant as we
have the unique opportunity to utilize our full-body autopsy capability in Zambia to address the yet-to-be
answered questions of whether there are KSHV tissue reservoirs, the cell types involved, and how HIV-1
infection and development of KS will impact these reservoirs, and simultaneously expand this capability to our
other SSA partner in Tanzania. Findings from this study may contribute to our understanding of KS recurrence
after treatment and identify the potential target locations for any future novel treatment/therapy that can
specifically eliminate KSHV infection and KS development.

## Key facts

- **NIH application ID:** 10909003
- **Project number:** 5U54CA277846-02
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** For Yue Tso
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $301,515
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909003

## Citation

> US National Institutes of Health, RePORTER application 10909003, Project 3 (5U54CA277846-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909003. Licensed CC0.

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