Candida-Host interactions: impact on the host pro- and anti-viral restrictions factors

念珠菌-宿主相互作用：对宿主亲病毒和抗病毒限制因素的影响

基本信息

批准号：
10324146
负责人：
Ramiro Mendonca Murata
金额：
$ 15.1万
依托单位：
EAST CAROLINA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10324146
关键词：
Acquired Immunodeficiency Syndrome Adult Affect Antiviral Agents Applications Grants CCL3 gene CCR5 gene Candida Candida albicans Candidiasis Cell Wall Cells Clinical Data Epithelial Cells Future Genes HIV HIV Infections HIV Receptors HIV Seropositivity HIV-1 Health Homeostasis Human Immune Immune response Immune system Immunocompromised Host Individual Infection Inflammatory Interferon-alpha Interferons Life Ligands Link Macrophage Inflammatory Protein-1 Malignant Neoplasms Mannans Mannose Molecular National Institute of Dental and Craniofacial Research Opportunistic Infections Oral Oral candidiasis Oral cavity Oropharyngeal Outcome Pathogenesis Pathway interactions Patients Pattern Pattern recognition receptor Phenotype Production Proteins Quality of life RANTES Reporting Risk Route Signal Pathway Signal Transduction Stromal Cell-Derived Factor 1 Structure TRIM5 gene Testing Tissues Transcriptional Regulation United States National Institutes of Health Up-Regulation Viral Viral Load result Virus Virus Diseases Yeasts base beta-Chemokines chemokine chemokine receptor co-infection cohort comorbidity cytokine fungus immune function improved insight macrophage member microorganism mutant mycobiome oral cavity epithelium oropharyngeal thrush pathogen receptor response therapy design transcription factor transmission process

Acquired Immunodeficiency Syndrome Adult Affect Antiviral Agents Applications Grants CCL3 gene CCR5 gene Candida Candida albicans Candidiasis Cell Wall Cells Clinical Data Epithelial Cells Future Genes HIV HIV Infections HIV Receptors HIV Seropositivity HIV-1 Health Homeostasis Human Immune Immune response Immune system Immunocompromised Host Individual Infection Inflammatory Interferon-alpha Interferons Life Ligands Link Macrophage Inflammatory Protein-1 Malignant Neoplasms Mannans Mannose Molecular National Institute of Dental and Craniofacial Research Opportunistic Infections Oral Oral candidiasis Oral cavity Oropharyngeal Outcome Pathogenesis Pathway interactions Patients Pattern Pattern recognition receptor Phenotype Production Proteins Quality of life RANTES Reporting Risk Route Signal Pathway Signal Transduction Stromal Cell-Derived Factor 1 Structure TRIM5 gene Testing Tissues Transcriptional Regulation United States National Institutes of Health Up-Regulation Viral Viral Load result Virus Virus Diseases Yeasts base beta-Chemokines chemokine chemokine receptor co-infection cohort comorbidity cytokine fungus immune function improved insight macrophage member microorganism mutant mycobiome oral cavity epithelium oropharyngeal thrush pathogen receptor response therapy design transcription factor transmission process

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项目摘要

The human immunodeficiency virus (HIV) is responsible for the acquired immunodeficiency syndrome (AIDS). The first cases of AIDS were reported in 1981 and it is one of the world's most serious health problems. The risk of adults becoming infected through the oral route appears to be relatively low and it is generally assumed that HIV transmission does not occur through casual oral contact, even among patients with high viral load. People with advanced HIV infection are vulnerable to life-threatening malignancies and opportunistic infections such as candidiasis. Oropharyngeal candidiasis affects up to 50% of untreated HIV-1 subjects and 90% of AIDS patients. Interestingly, HIV-1 directly interacts with Candida spp and this interaction abrogates the production of HIV-1 by infected macrophages. Our preliminary data provide new insights into the mechanisms by which Candida albicans acts against HIV-1. The putative pathways by which C. albicans affects HIV-1 infection involve the upregulation of cc-chemokines. Therefore, the hypothesis of the proposed study is that C. albicans are involved in the inhibition of HIV pathogenesis. To explore our hypothesis, we propose to: 1) Elucidate the specific host cell-signaling pathways induced by C. albicans PAMPs relevant to production of anti-HIV cc-chemokines and 2) Determine how C. albicans PAMPs driven responses impact the host antiviral restrictions factors.

人类免疫缺陷病毒（HIV）负责获得的免疫缺陷综合征（AIDS）。第一批艾滋病案件是在1981年报告的，它是世界上最严重的健康问题之一。风险通过口头途径感染的成年人似乎相对较低，通常认为即使在高病毒负荷的患者中，HIV传播也不会通过休闲的口服接触进行。人们患有晚期艾滋病毒感染容易受到威胁生命的恶性肿瘤和机会性感染的影响作为念珠菌病。口咽念珠菌病影响多达50％的未经治疗的HIV-1受试者和90％的艾滋病患者。有趣的是，HIV-1直接与Candida SPP相互作用，这种相互作用消除了生产感染巨噬细胞的HIV-1。我们的初步数据提供了有关其机制的新见解白色念珠菌对HIV-1作用。白色念珠菌影响HIV-1感染的推定途径涉及CC化学因子的上调。因此，拟议的研究的假设是白色念珠菌参与抑制HIV发病机理。为了探讨我们的假设，我们建议：1）阐明白色念珠菌pamps诱导的特定宿主细胞信号途径与抗HIV CC-emokines的产生相关，2）确定白色念珠菌pamps驱动反应如何影响宿主抗病毒病毒限制。因素。