Oral Exposure and Transmission of HIV

描述(申请人提供)：绝大多数新获得的艾滋病毒感染是在暴露于粘膜表面的艾滋病毒感染性之后发生的。口腔接触艾滋病毒血清阳性捐赠者的精液可导致原发艾滋病毒感染。扁桃体器官培养系统已经被开发出来，以研究艾滋病毒在口腔中传播的细胞和分子机制。通过使用HIV感染者的精液作为HIV感染源，就有可能构建一个通过粘膜表面传播HIV的真实模型。这项建议的主要目标是将精液中的HIV感染性(HIV病毒粒子或HIV感染细胞)应用于完整的扁桃体上皮表面，以跟踪暴露后HIV感染性的扩散，然后监测原发HIV感染的建立。利用活组织的延时共聚焦显微镜已经建立了新的程序，允许直接可视化发生在暴露的上皮表面及其下方的事件。通过将共聚焦显微镜与高分辨率单细胞原位杂交和免疫细胞化学检测方法相结合，可以得出艾滋病毒传播的综合表现，这些方法是从相同组织的横切切片进行的。清楚地了解支持暴露在暴露的粘膜表面的艾滋病毒传播的细胞和分子事件，以及认识到精液引起的变化，将大大有助于制定保护战略，以减少艾滋病毒的总体传播频率。

DESCRIPTION (provided by applicant): The vast majority of newly acquired HIV infections develop following exposure to HIV infectivity at mucosal surfaces. Oral exposure to semen from HIV seropositive donors can lead to primary HIV infection. Tonsil organ culture systems have been developed in order to investigate the cellular and molecular mechanisms that underlie HIV transmission in the oral cavity. By using semen from HIV-infected donors as a source of HIV infectivity, it is possible to construct an authentic model of HIV transmission across mucosal surfaces. The major goal of this proposal is to apply HIV infectivity in semen (HIV virions or HIV-infected cells) to intact tonsillar epithelial surfaces to track the dispersal of HIV infectivity immediately after exposure and then monitor the establishment of primary HIV infection. Novel procedures have been established for time-lapse confocal microscopy with live tissue that allow direct visualization of events occurring at, and immediately below the exposed epithelial surfaces. A comprehensive representation of HIV transmission can be derived by combining confocal microscopy with high resolution single-cell in situ hybridization and immunocytochemical detection methods, performed with transverse sections cut from the same tissues. Clear understanding of the cellular and molecular events that support HIV transmission at exposed mucosal surfaces, and recognition of changes induced by semen, will contribute significantly towards the development of protective strategies to reduce the overall frequency of HIV transmission.