# Use of a non-human primate model to define the role of T cell immune responses in persistent Kaposi sarcoma-associated herpesvirus infection and Kaposi sarcoma pathogenesis

> **NIH NIH R21** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2024 · $326,516

## Abstract

PROJECT ABSTRACT
Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of several human malignancies including
Kaposi sarcoma (KS). KS is the most common KSHV-associated malignancy, with >44,000 new cases reported
worldwide each year. The population most vulnerable to KSHV/KS are immunocompromised individuals such
as people infected with HIV. Individuals with HIV/AIDS have a higher risk of developing KS when compared to
HIV-negative individuals. The adaptive T cell immune response, especially CD4+ and CD8+ T cells, has been
shown to play a crucial role in KSHV infection and subsequent KS pathogenesis. Although correlations between
CD4+ and CD8+ T cell levels and KS development have been observed, this relationship has not been
experimentally validated due to the lack of a suitable animal model. The recent development of the common
marmoset (Callithrix jacchus) as a non-human primate (NHP) model that is susceptible to KSHV infection and
capable of developing KS-like lesions under immunosuppression opens new frontiers to experimentally validate
the role immune cells play in KS development. Thus, our objective is to define the role of reduced CD4+ and
CD8+ T cell levels in persistent KSHV infection and subsequent KS pathogenesis in the marmoset NHP model.
Anti-CD4 and anti-CD8 monoclonal antibodies (mAbs) have been used to deplete T cells and induce
immunosuppression in both murine and NHP animal models, enabling study of CD4+/CD8+ T cells in controlling
replication of several viruses. To avoid any adverse responses to murine mAbs when administered into
marmosets, we will chimerize (murine-marmoset) anti-CD4/CD8 mAbs and characterize their biochemical and
pharmacokinetic properties in vitro and in mice, then we will determine the effects of antibody-mediated T cell
depletion on various immune cell populations (Aim 1). We will then challenge immunosuppressed marmosets
with KSHV.219 virus and determine the extent to which antibody-mediated depletion of CD4+ and/or CD8+ T
cells enables persistent KSHV infection and KS pathogenesis in immunocompromised marmosets (Aim 2). The
successful completion of this project will validate the common marmoset as a tool for understanding the etiology
of KS and uncover the critical role that CD4+ and/or CD8+ T cell depletion plays in allowing persistent KSHV
infection and subsequent KS pathogenesis in immunocompromised animals.

## Key facts

- **NIH application ID:** 10770565
- **Project number:** 5R21AI168750-02
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Lorraine Zvichapera Mutsvunguma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $326,516
- **Award type:** 5
- **Project period:** 2023-02-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770565

## Citation

> US National Institutes of Health, RePORTER application 10770565, Use of a non-human primate model to define the role of T cell immune responses in persistent Kaposi sarcoma-associated herpesvirus infection and Kaposi sarcoma pathogenesis (5R21AI168750-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10770565. Licensed CC0.

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