# Periodontal bacteria enhance oral KSHV pathogenesis and Kaposi's Sarcoma development in HIV + patients

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2021 · $372,400

## Abstract

PROJECT ABSTRACT
Kaposi's sarcoma (KS) remains the most common tumor arising in patients with HIV/AIDS, and involvement of
the oral cavity represents one of the most common clinical manifestations of this tumor. HIV infection incurs an
increased risk for periodontal diseases and oral carriage from a variety of pathogenic bacteria. However,
whether interactions involving periodontal bacteria and oncogenic viruses in the local environment facilitate
replication or maintenance of these viruses in the oral cavity remains largely unknown. Our published and
preliminary data indicate that incubation of human primary oral cells with two prototypical pathogen-associated
molecular patterns (PAMPs) produced by prominent periodontal bacteria—lipoteichoic acid (LTA) from
Staphylococcus aureus (Sa) and lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg)—increases
initial viral entry and subsequent latent gene expression during de novo KSHV infection. Moreover, LTA and
LPS up-regulate one of cellular receptors for KSHV entry, Heparan sulfate proteoglycan (HSPG) and increase
reactive oxygen species (ROS) production as co-factor contributed to KSHV infection. Additionally, we found
that conditioned medium from Sa and Pg culture or bacterial PAMPs induced viral lytic reactivation from
latently infected oral cells through regulation of viral microRNAs expression, promoting virus dissemination. For
clinical relevance, we found a high infection and co-infection rate of Sa, Pg and KSHV in the oral cavity of our
cohort of HIV+ patients, and found higher levels of salivary ROS, host antioxidant factors and bacterial
LTA/LPS from HIV+/KSHV+ patients than those HIV+/KSHV- ones. Based on these data, we hypothesize that
periodontal bacteria or their PAMPs may facilitate initial KSHV infection, replication and dissemination
in the oral cavity of HIV+ patients through multiple host and viral factors, and ultimately promote oral
KS development. To address this hypothesis, we propose the following specific aims including both clinical
and basic studies: 1) Determine the clinical relevance and correlations between host salivary antioxidant
factors, specific bacterial carriage/PAMPs levels, and KSHV oral shedding in HIV+ patients. 2) Identify the
mechanisms through which periodontal bacteria or their PAMPs facilitate KSHV initial infection and viral lytic
reactivation, two important steps necessary for KS development. Through these efforts, we can better
understand how pathogens co-infection can promote virus-associated cancer development in oral unique niche
of immunocompromised patients. Our results will also provide the framework for the development of clinical
trials evaluating the strategies interfering with host-bacteria-virus interaction (e.g. specific antibiotics, targeting
TLRs-ROS axis or viral microRNAs synthesis) for their abilities to reduce or prevent oral KSHV infection and
KS progression in HIV+ patients.

## Key facts

- **NIH application ID:** 10236358
- **Project number:** 5R01CA228166-04
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** James Craig Forrest
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $372,400
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236358

## Citation

> US National Institutes of Health, RePORTER application 10236358, Periodontal bacteria enhance oral KSHV pathogenesis and Kaposi's Sarcoma development in HIV + patients (5R01CA228166-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10236358. Licensed CC0.

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