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

• 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
• 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

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.

人体免疫缺陷病毒（HIV）是导致获得性免疫缺陷综合症（AIDS）的罪魁祸首。 1981年报告了第一例艾滋病病例，它是世界上最严重的健康问题之一。风险 成年人通过口服途径感染的比例似乎相对较低，一般认为， 即使在病毒载量高的患者中，也不会通过偶然的口腔接触传播艾滋病毒。人 晚期HIV感染者易患危及生命的恶性肿瘤和机会性感染， 念珠菌病口咽念珠菌病影响高达50%的未经治疗的HIV-1受试者和90%的AIDS受试者 患者有趣的是，HIV-1直接与念珠菌相互作用，这种相互作用消除了病毒的产生 HIV-1感染的巨噬细胞我们的初步数据提供了新的见解的机制， 白色念珠菌对HIV-1起作用。C.白色念珠菌影响HIV-1感染 涉及α-趋化因子的上调。因此，本研究假设C.白色 参与抑制HIV发病机制。为了探索我们的假设，我们建议：1）阐明 特异性的宿主细胞信号传导途径。与抗HIV α-趋化因子的产生相关的白色念珠菌PAMP和2）确定C.白念珠菌PAMP驱动的应答影响宿主抗病毒限制 因素