# Unmasking the roles of viral glycoproteins in oral transmission of KSHV

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2022 · $199,999

## Abstract

PROJECT SUMMARY This application is being submitted in response to the Notice of Special Interest (NOSI)
identified as “NOT-CA-22-057.” More than 44,000 new cases of Kaposi sarcoma (KS) are reported globally each
year, 84% of which occur in Africa. This and other Kaposi sarcoma-associated herpesvirus (KSHV)-induced
malignancies predominate in people with acquired or iatrogenic immunodeficiencies. Although KSHV can be
detected in other human body fluids, its frequent detection in saliva in groups both with and without risk of
sexually transmitted infections (e.g., children) suggests that the oral cavity is the site of primary acquisition.
However, the mechanism of KSHV oral transmission in vivo, particularly the critical viral envelope
glycoproteins (gps) required for viral entry, remains unresolved. Several KSHV–host interactions have
been identified, but all prior experiments were performed in vitro and have not been validated in vivo due to prior
lack of an appropriate animal model. Through collaboration with the Wisconsin National Primate Research
Center, our laboratory has access to the common marmoset (Callithrix jacchus, CJ), a recently developed KSHV
non-human primate model that is susceptible to KSHV oral infection, and under immunosuppression acquires
KS-like skin lesions. The objective of this application is to elucidate the minimum gps required to initiate primary
oral infection in vivo, as a prerequisite to selecting key gps for developing an effective prophylactic vaccine
candidate. This application builds on Dr. Ogembo’s recently completed NCI K01 CA184388-05 research on
KSHV entry mechanisms and vaccine development. Recently, we showed that in vitro, the KSHV glycoprotein
gH/gL is essential for viral infection of epithelial, endothelial, and fibroblasts cells, but not B cells. Notably, we
and others have also shown that both monoclonal and polyclonal Abs to KSHV glycoproteins gB, gH/gL, and
gpK8.1, can neutralize KSHV infection of diverse permissive human cells in vitro. Building on this success, we
generated KSHV deletion mutants lacking the four glycoproteins thought to be critical for viral entry (gB, gH/gL,
gpK8.1) and various monoclonal antibodies specific to these gps. In this project, we will use human ex vivo
samples and the CJ KSHV model to test the hypothesis that gB and gH/gL are critical for KSHV in vivo oral
transmission. The premise of our proposal is built on strong evidence that 1) KSHV can infect CJ, which develop
KS-like skin lesions, and 2) Abs against the KSHV glycoproteins gB and gH/gL can neutralize KSHV infection in
vitro and ex vivo. Furthermore, the permissiveness to KSHV infection of human cells ex vivo and CJ makes these
platforms ideal to test the KSHV gp requirements for infection. Successful completion of the proposed study will
elucidate the minimum KSHV gps required for primary infection in ex vivo and in vivo models, advancing our
long-term goal of defining the initial steps in KSHV infection of hum...

## Key facts

- **NIH application ID:** 10627167
- **Project number:** 3R01CA264911-02S2
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Javier Gordon Ogembo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,999
- **Award type:** 3
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10627167

## Citation

> US National Institutes of Health, RePORTER application 10627167, Unmasking the roles of viral glycoproteins in oral transmission of KSHV (3R01CA264911-02S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10627167. Licensed CC0.

---

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