# Impacts of antiretroviral therapy on oral cavity homeostasis in an FIV animal model

> **NIH NIH R21** · COLORADO STATE UNIVERSITY · 2021 · $189,550

## Abstract

Program Summary / Abstract
HIV infection results in well-documented changes to gut-associated lymphoid tissue, but few studies have evaluated
whether similar mucosal immunological dysfunction occurs in the oral cavity. Moreover, despite growing evidence of the
importance of the microbiome in maintaining health and local homeostasis, the impacts of HIV on oral microbial
communities and the mechanisms contributing to immunodeficiency-induced periodontitis and systemic
inflammation remain poorly defined. Studies of these phenomena have been hampered by lack of a suitable animal
model, as commonly used animal models for HIV (SIV/SHIV infections of non-human primates and HIV infections in
humanized mice) do not reliably result in oral disease. Feline immunodeficiency virus (FIV) is a T cell tropic lentivirus
that causes AIDS in its natural host, and results in immunological dysfunctions and opportunistic infections similar to
HIV-AIDS. Relevant to this proposal, and similar to HIV infections, periodontal and oral inflammatory disease occurs
in the majority of FIV-infected animals. Our preliminary studies demonstrate that FIV infection of domestic cats is
associated with: (1) oral dysbiosis, with a marked loss of microbial diversity during FIV-associated periodontitis; and, (2)
changes in salivary cytokine levels, even in the absence of FIV clinical oral disease. Furthermore, an easily administered
cART protocol efficacious against SIV in macaques strongly inhibits FIV growth in vitro. Development of a well-
tolerated, effective cART is an important next step in developing the FIV in vivo model for follow-on studies of
HIV disease. We therefore propose to validate FIV as a relevant model for HIV-associated oral disease by assessing
stepwise pathology that occurs in the presence and absence of FIV viral replication. We will monitor clinical status, oral
microbiota, local and systemic viral burden, and immune profile during systemic treatment in the presence and absence of
a novel cART therapy. Aim 1 will assess the impact of cART in controlling oral cavity viral replication and subsequent
impacts on oral microbiome and local inflammation during acute and subacute infection. Aim 2 will apply causal
modeling (Structural Equation Modeling) and model selection to determine the direct and indirect mechanistic basis of
FIV-induced periodontal disease in the presence and absence of cART. We have assembled an experienced team of
investigators to conduct the proposed experiments and modeling, and will work with experts in HIV oral disease to
translate our findings into hypothesis-based approaches for new therapeutic interventions for HIV-associated oral
disease. Further our work will interrogate local and systemic immune deficits related to oral cavity viral replication
and infection.

## Key facts

- **NIH application ID:** 10228085
- **Project number:** 5R21DE029733-02
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** SUE VANDEWOUDE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,550
- **Award type:** 5
- **Project period:** 2020-08-03 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228085

## Citation

> US National Institutes of Health, RePORTER application 10228085, Impacts of antiretroviral therapy on oral cavity homeostasis in an FIV animal model (5R21DE029733-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10228085. Licensed CC0.

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