AIDS-associated viral infections in human oral tissues

人体口腔组织中与艾滋病相关的病毒感染

• 批准号: 6945043
• 负责人: Fenyong Liu
• 金额: $ 34.2万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6945043
• 关键词: clinical research; cytomegalovirus; gene mutation; genetic models; human immunodeficiency virus; human tissue; model design /development; open reading frames; opportunistic infections; oral mucosa; tissue /cell culture; virus genetics; virus infection mechanism; virus replication; virus virus interaction

DESCRIPTION (provided by applicant): Oral infection represents an important route of human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) transmission, leading to global consequences. HCMV infection is among the most common causes of oral diseases associated with AIDS patients. Furthermore, HIV and HCMV are found in oral tissues and their interaction is believed to play an important role for their successful oral transmission as well as for the development of viral-induced oral diseases. However, little is currently known about the mechanism of HCMV and HIV oral infections, partially because these infections are primarily limited to human cells, and few cultured tissue or animal models for studying HCMV and HTV infections in oral mucosa have been reported. Recent in vitro studies indicate that productive HIV infection occurs in normal human oral keratinocytes and is enhanced in the presence of environmental factors in oral mucosa, such as alcohol, which up-regulates CXCR4 receptor expression. Our preliminary studies suggest that HCMV productively infects cultured human gingival and buccal tissues and significantly enhances HIV infection in cultured oral mucosa. The overall objective of this proposed research is to develop human gingival and buccal tissue culture model and use these cultured tissues to study the infection of HCMV and HIV and their interactions in oral mucosa. In the initial part of the proposed study, in vitro human buccal and gingival tissue culture models will be developed. Tissues will then be infected with a library of HCMV mutants with deletion of a single viral open reading frame. Viral mutants that are defective in growth in cultured tissues will be identified and characterized. Furthermore, the function of HCMV determinants essential for viral oral infection will be studied. Finally, tissues will be infected with HIV in the absence and presence of different HCMV mutants, and the mechanism of how HIV oral infection is affected by HCMV will be investigated. The proposed research will lead to the development of new tissue culture models to study HIV and HCMV infection in oral mucosa. These studies will also identify viral genes required for HCMV replication in oral mucosa and investigate the mechanism of HIV-HCMV interactions in oral cavity. The results will provide insight into the mechanism of HCMV and HIV infection in oral mucosa and facilitate the development of novel strategies for treatment and prevention of the transmission as well as infections of these viruses in oral cavity.

描述（由申请人提供）：口腔感染代表了人类免疫缺陷病毒（HIV）和人类巨细胞病毒（HCMV）的重要途径，导致全球后果。 HCMV感染是与艾滋病患者相关的口腔疾病最常见原因之一。此外，在口腔组织中发现了艾滋病毒和HCMV，据信它们的相互作用对于成功的口服传播以及病毒诱发的口腔疾病的发展起着重要作用。但是，目前对HCMV和HIV口腔感染的机制知之甚少，部分是因为这些感染主要限于人类细胞，并且很少有用于研究口腔粘膜中HCMV和HTV感染的培养组织或动物模型。最近的体外研究表明，在正常的人口服角质形成细胞中，生产性HIV感染发生，并且在口服粘膜中存在环境因素（例如酒精）的存在下，会增强，例如酗酒，这会上调CXCR4受体表达。我们的初步研究表明，HCMV有效地感染了培养的人类牙龈和颊组织，并显着增强了培养的口服粘膜中的HIV感染。这项拟议的研究的总体目的是开发人类牙龈和颊组织培养模型，并使用这些培养的​​组织研究HCMV和HIV的感染及其在口服粘膜中的相互作用。 在拟议的研究的最初部分中，将开发体外人类颊和牙龈组织培养模型。然后，组织将被HCMV突变体的库感染，并删除单个病毒开放式阅读框架。将鉴定和表征在培养组织生长中有缺陷的病毒突变体。此外，将研究HCMV决定因素对病毒口腔感染必不可少的功能。最后，将在不存在和存在不同的HCMV突变体的情况下感染HIV，并研究HCMV的HIV口腔感染的机制。拟议的研究将导致开发新的组织培养模型，以研究口腔粘膜中的HIV和HCMV感染。这些研究还将确定口服粘膜中HCMV复制所需的病毒基因，并研究口腔中HIV-HCMV相互作用的机制。该结果将洞悉口腔粘膜中HCMV和HIV感染的机制，并促进开发用于治疗和预防传播的新型策略，以及这些病毒在口腔中的感染。