HUMAN TISSUE MODEL FOR HETEROSEXUAL HIV INFECTION

异性 HIV 感染的人体组织模型

• 批准号: 6156165
• 负责人: MITCHELL KLAUSNER
• 金额: $ 28.54万
• 依托单位: MATTEK CORPORATION
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6156165
• 关键词: HIV infections; Langerhans' cell; disease /disorder model; heterosexuals; human tissue; immunocytochemistry; method development; model design /development; postmortem; tissue /cell culture; transmission electron microscopy; vagina; virus infection mechanism

During 1998, 75,000 North Americans and Western Europeans became newly infected with human immunodeficiency virus (HIV), the virus that leads to acquired immune deficiency syndrome (AIDS). Worldwide, 6 million new infections occurred during 1998, bringing the total number of people living with HIV/AIDS to 33.4 million. Heterosexual transmission is now responsible for the large majority of new infections worldwide. Although HIV transmission can often be prevented by condom use, there is considerable interest in developing female controlled methods to prevent HIV transmission since reliable, consistent condom use does not always occur. In addition, since the mechanisms of vaginal transmission of HIV are poorly understood a human based model to study HIV infection, transmission, and the prevention thereof would be of great utility in combating the worldwide HIV epidemic. Phase I research will develop an immuno-competent model of normal human vaginal epithelial tissue (HVT). Normal vaginal epithelial (VE) cells will be harvested, expanded in monolayer culture, and cryopreserved. New cell culture methods will be applied to induce VE cells to form a differentiated structure, which mimics in vivo VE tissue and Langerhans cells (LC) will be incorporated therein. The tissue will be characterized in terms of morphology, ultrastructure, and phenotype. Finally, whether HIV will infect the HVT according to mechanisms known to occur in vivo will be investigated. PROPOSED COMMERCIAL APPLICATION: The proposed HVT model will provide the pharmaceutical industry with a reproducible, cost-effective in vitro system to assist in the development of new viricides and microicides aimed at preventing sexurally transmitted diseases (STD), such as HIV. In addition, the human cell based model will avoid species extrapolation and will likely yield new insight into the mechanisms of heterosexual infection/transmission of HIV, and hence suggest novel prophylactic measures of prevention.

在1998年期间，75 000名北美和西欧人成为新的 感染人类免疫缺陷病毒（HIV），这种病毒导致 获得性免疫缺陷综合症（艾滋病）。全球新增600万感染病例 1998年，艾滋病毒/艾滋病感染者的总人数达到了2000人。 33.4万 异性性传播现在是大多数艾滋病的原因。 全球新感染虽然艾滋病毒的传播通常可以通过以下方式预防： 避孕套的使用，有相当大的兴趣，发展女性控制 预防艾滋病毒传播的方法，因为可靠、一致的避孕套使用 并不总是发生。此外，由于阴道传播的机制， 艾滋病毒是一种基于人类的研究艾滋病毒感染的模型， 传播，并防止其传播将是非常有用的， 全球艾滋病流行。 I期研究将开发一种免疫活性正常人阴道模型， 上皮组织（HVT）。正常的阴道上皮（VE）细胞将是 收获，在单层培养中扩增，并冷冻保存。新的细胞培养 将应用方法诱导VE细胞形成分化结构， 其模拟体内VE组织和朗格汉斯细胞（LC 在其中组织将在形态学方面进行表征， 超微结构和表型。最后，艾滋病毒是否会感染HVT 根据已知的体内发生的机制，将进行研究。 拟定商业应用： 所提出的HVT模型将为制药行业提供一种可重复的， 成本效益高的体外系统，以协助开发新的杀病毒剂和杀微生物剂 旨在预防性传播疾病（STD），如艾滋病毒。此外该 基于人类细胞模型将避免物种外推，并可能产生新的见解 艾滋病毒的异性感染/传播机制，因此建议 新的预防措施。