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

抗逆转录病毒治疗对 FIV 动物模型口腔稳态的影响

基本信息

批准号：
10228085
负责人：
SUE VANDEWOUDE
金额：
$ 18.96万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-03 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10228085
关键词：
AIDS/HIV problem Acquired Immunodeficiency Syndrome Acute Animal Model Animals Bacterial Translocation Biological Models Chronic Chronic Gingivitis Clinical Clinical Trials Communities Controlled Study Data Data Set Development Diet Disease Dysplasia Environment Equation Exposure to Family Felidae Feline Immunodeficiency Virus Felis catus Formulation Future Gastrointestinal tract structure Gingivitis Goals Growth Gut associated lymphoid tissue HIV HIV Infections Health Homeostasis Human Immune Immune System Diseases Immunologic Deficiency Syndromes Immunologics In Vitro Infection Inflammation Inflammatory Laboratories Lentivirus Lymphoid Tissue Macaca Microbiology Modeling Molecular Monitor Mouth Diseases Mucous Membrane Opportunistic Infections Oral Oral Manifestations Oral Pathology Oral cavity Oral mucous membrane structure Outcome Pathology Pathway interactions Patients Periodontal Diseases Periodontitis Personal Satisfaction Physiological Protocols documentation Publishing Reporting Research Personnel Risk Role SIV Salivary Sampling Statistical Models Structure Systemic disease T-Lymphocyte Tenofovir Testing Therapeutic Therapeutic Intervention TimeLine Translating Variant Viral Viral Load result Virus Diseases Virus Replication Work analog antiretroviral therapy base biosecurity causal model cytokine dysbiosis emtricitabine experience experimental study germ free condition humanized SCID mouse humanized mouse immune activation immune function in vivo Model mathematical model microbial microbial community microbiome microbiome analysis microbiome research mouse model nonhuman primate novel novel therapeutic intervention opportunistic pathogen oral HIV oral condition oral microbial community oral microbiome programs response simian human immunodeficiency virus systemic inflammatory response

项目摘要

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.

节目摘要/摘要

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Combination Antiretroviral Therapy and Immunophenotype of Feline Immunodeficiency Virus.

DOI：
10.3390/v15040822
发表时间：
2023-03-24
期刊：
Viruses
影响因子：
0
作者：
Kim J;Behzadi ES;Nehring M;Carver S;Cowan SR;Conry MK;Rawlinson JE;VandeWoude S;Miller CA
通讯作者：
Miller CA