# Models for KHSV transmission and its inhibition

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2022 · $416,558

## Abstract

ABSTRACT
Kaposi's sarcoma (KS) is a highly prevalent malignancy in sub-Saharan Africa. This cancer,
with Kaposi's sarcoma herpesvirus (KSHV) as the etiologic agent, is at increased incidence in
HIV-1 infected patients despite antiretroviral (ART) suppression of HIV-1 viral load. It also
occurs as an aggressive tumor in the HIV-negative population. Our team has been studying KS
and KSHV transmission in KS endemic countries and we have shown that KSHV infection is
acquired predominantly in early childhood, HIV-1 infection is a major risk factor, and that
mucosal exposure to infectious saliva is the likely mechanism of transmission. More recently,
our results from Zambia and Tanzania demonstrated that high titer neutwith symptomatic KS as
opposed to infected asymptomatic individuals, suggesting that nAb is not a correlate of KS
protection. Thus, much like in the HIV-1 virus-host interaction, it appears that KSHV nAb cannot
prevent disease after long-term chronic infection. However, the prophylactic capacity ofralizing
Ab responses (nAb) develop primarily in individuals passively administered broadly nAb has
been demonstrated in HIV-1/SIV infectious challenge models; whereas, the ability of pre-
existing nAb to prevent KSHV transmission is untested. In addition, while the in vitro KSHV
entry process has been studied in some depth, the precise viral and cellular interactions
involved in KSHV at the tissue level, have not been clearly elucidated. In part, this knowledge
gap results from the lack of an in vivo model of human KSHV transmission. The proposed
project applies our team's long-term experience with KS, KSHV, human KSHV Ab responses,
and KSHV infection in a
humanized mouse model that we have developed, to address the knowledge gap posed by
KSHV transmission and dissemination. Our overall objective is to identify immune response(s)
that can protect against KSHV infection and transmission, and thereby, prevent KS. Our
hypothesis is that KSHV nAb can be protective against KSHV transmission in ex vivo human
organotypic tissue models and in a humanized mouse model of KSHV infection. The hypothesis
will be tested with 3 specific aims: 1) Develop organotypic oral and vaginal epithelial culture
models to understand KSHV transmission dynamics and to test whether sera with high nAb titer
prevents trans-epithelial KSHV infection; 2) test whether KSHV nAb is protective in a humanized
BLT-mouse model of mucosal and blood exposure, infection and dissemination of KHSV, and 3)
isolation of human monoclonal KSHV nAb and characterization of their impact on KSHV
transmission. This project will clarify the mechanisms of KSHV transmission and dissemination,
and lay the foundations for strategies to develop a vaccine to prevent KSHV infection.
Ultimately, such studies will expand our capacity to prevent KSHV infection and associated
neoplasms.

## Key facts

- **NIH application ID:** 10527645
- **Project number:** 7R01CA239591-03
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** John T. West
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $416,558
- **Award type:** 7
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527645

## Citation

> US National Institutes of Health, RePORTER application 10527645, Models for KHSV transmission and its inhibition (7R01CA239591-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10527645. Licensed CC0.

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