杨瑜，张晓燕,2

1 上海市公共卫生临床中心，上海 201508

2 复旦大学生物医学研究院，上海 201508

人体黏膜活组织模型在HIV-1性传播途径感染中的应用

杨瑜1，张晓燕1,2

1 上海市公共卫生临床中心，上海 201508

2 复旦大学生物医学研究院，上海 201508

性传播途径已经成为全球人免疫缺陷病毒1型 (Human immunodeficiency virus type 1，HIV-1) 传播的主要方式。对HIV-1黏膜感染机制的深入理解，将有助于研发新型有效的生物技术阻断其感染和传播。目前，HIV-1黏膜感染机制的研究主要依赖于体外细胞培养和灵长类动物模型。近年来，一种新型黏膜活组织模型 (包括人体生殖道或肠道黏膜等组织) 的建立，可再现HIV-1突破黏膜屏障进入基底侧的生物学过程，适用于 HIV-1黏膜感染机制与黏膜局部感染阻断生物技术的临床前有效性评价研究。以下主要阐述了该模型的组织类型、技术特点以及在 HIV-1性途径感染机制与阻断技术研究中的进展，并结合本实验室工作对其新的应用进行了展望。

人免疫缺陷病毒1型，性传播，组织培养，模型应用

Abstract:Sexual transmission has become the major route of acquiring human immunodeficiency virus type 1 (HIV-1) globally.Understanding the mechanism of HIV-1 mucosal infection will be helpful for development of new effective strategies to block HIV-1 mucosal transmission. Currently, study of the mechanism of HIV-1 mucosal infection majorly depends on in vitro cell culture systems and non-human primate animal models. Recently, a novel tissue explant model (including human vaginal-genital and colorectal tissue) was established, which could elucidate the biological process of HIV-1 mucosal infection from crossing over the membrane to reaching the basal. Therefore, the model can be applied to the study of mechanism, as well as the safety and efficacy evaluation in pre-clinical study of biomedical prevention strategies. In this review, we summarized the recent progress about human mucosal explants model including the sources of tissues, technical characteristics and their application to study the mechanism of HIV-1 sexual transmission and evaluation of prevention strategies. Based on our recent study results, we also provided our opinions aboutdevelopment of novel explant models and their application.

Keywords:human immunodeficiency virus type 1 (HIV-1), sexual transmission, mucosal infection, explants culture model

在全世界范围内有将近一半的 HIV-1感染者是妇女，她们大多通过异性性接触而感染HIV-1[1]；另一方面经同性性接触而感染 HIV-1的男男同性恋人群 (Men who have sex with men，MSM) 的比例近年来也在迅速地增长[2]；总体来看，经性接触传播已经成为全球HIV-1疫情难以控制的主要原因。我国HIV-1新发感染上升的趋势依然难以遏制。2007年新发感染者中56.9%为经性途径感染，2009年已经上升为70%，性传播已成为我国HIV-1感染与传播的主要途径，促使HIV-1从高危人群向一般人群扩散[3]。……