Oral Exposure and Transmission of HIV

描述（由申请人提供）：绝大多数新获得的HIV感染是在暴露于具有HIV传染性的粘膜表面后发生的。口腔接触HIV血清阳性供者的精液可导致原发性HIV感染。扁桃体器官培养系统的发展是为了研究HIV在口腔传播的细胞和分子机制。通过使用来自HIV感染供体的精液作为HIV传染性的来源，有可能构建一个真实的HIV在粘膜表面传播的模型。本研究的主要目标是将精液中的HIV传染性（HIV病毒或HIV感染细胞）应用于完整的扁桃体上皮表面，在暴露后立即追踪HIV传染性的扩散，然后监测原发性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，可以直接观察在暴露的上皮表面及其下方发生的事件。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，从同一组织中切割横切面，可以获得HIV传播的全面代表。清楚地了解在暴露的粘膜表面支持HIV传播的细胞和分子事件，并识别精液引起的变化，将有助于制定保护策略，以减少HIV传播的总体频率。

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.