EBV PATHOGENESIS IN HIV-ASSOCIATED HAIRY LEUKOPLAKIA

HIV 相关毛状白斑中的 EBV 发病机制

• 批准号: 6523843
• 负责人: DENNIS M WALLING
• 金额: $ 26.1万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6523843
• 关键词: Epstein Barr virus; HIV infections; antiviral agents; biopsy; clinical research; gastrointestinal epithelium; gene expression; genetic polymorphism; genetic promoter element; genetic transcription; human subject; in situ hybridization; latent virus infection; molecular pathology; opportunistic infections; oral leukoplakia; polymerase chain reaction; southern blotting; tongue; transcription factor; virus genetics; virus infection mechanism; virus protein; virus replication; virus virus interaction

Hairy leukoplakia (HLP) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected individuals. HLP occurs on the lateral tongue and is caused by the Epstein-Barr virus (EBV). HLP is remarkable as the only pathologic manifestation of productive EBV infection and as the only non-malignant lesion of epithelial cell EBV infection. HLP offers insight into the mechanisms of EBV persistence and the role of specific EBV gene products in HIV-associated EBV pathogenesis. Three hypotheses will be tested: 1) That tongue epithelial cells are a second reservoir of persistent EBV infection in HIV-infected individuals. 2) That HLP results from a unique co-expression of both latent and productive EBV genes. 3) That novel molecular mechanisms regulate the unique pattern of EBV gene expression seen in HLP. In a clinical study protocol, HIV-infected volunteers with HLP will be treated with antiviral therapy to inhibit EBV replication and induce BV latency. Subsequent withdrawal of antiviral therapy will permit EBV reactivation. Tongue and blood lymphocyte tissues will be collected before, during, and after antiviral therapy. Molecular studies will investigate the molecular biology and epidemiology of EBV latency and reactivation. The role of gene expression in EBV pathogenesis will be investigated, including the functional consequences of EBV gene sequence variation and genetic recombination in HLP. Finally, the role of HIV-EBV interaction in HLP pathogenesis will be investigated. The results of this study will elucidate molecular mechanisms of EBV pathogenesis in HLP applicable to other EBV-associated diseases, including nasopharyngeal carcinoma and HIV-associated lymphomas.

毛发白斑病（HLP）是人类免疫缺陷病毒（HIV）感染者常见的机会性感染. HLP发生在舌侧，由EB病毒（EBV）引起。HLP是EBV感染的唯一病理表现，也是EBV感染上皮细胞的唯一非恶性病变。HLP提供了深入了解EBV持续存在的机制和特定EBV基因产物在HIV相关EBV发病机制中的作用。将测试三个假设：1）舌上皮细胞是HIV感染个体中持续性EBV感染的第二储库。2)该HLP由潜伏性和生产性EBV基因的独特共表达引起。3)新的分子机制调节HLP中观察到的EBV基因表达的独特模式。在临床研究方案中，患有HLP的HIV感染志愿者将接受抗病毒治疗以抑制EBV复制并诱导BV潜伏期。随后停止抗病毒治疗将允许EBV重新激活。将在抗病毒治疗前、治疗期间和治疗后采集舌和血液淋巴细胞组织。分子研究将调查EB病毒潜伏期和再活化的分子生物学和流行病学。基因表达在EBV发病机制中的作用将被研究，包括EBV基因序列变异和遗传重组在HLP中的功能后果。最后，将研究HIV-EBV相互作用在HLP发病机制中的作用。本研究的结果将阐明HLP中EBV致病的分子机制，适用于其他EBV相关疾病，包括鼻咽癌和HIV相关淋巴瘤。