巴斯德所揭示HIV-1黏膜感染（性传播）新机制 - 中国病毒学论坛|我们一直在坚持！

性传播是当前HIV-1最主要的传播方式。生殖道黏膜、直肠或口腔黏膜组织为HIV-1的性传播提供了主要的感染位点，HIV-1黏膜感染过程尚不清楚。一般认为，亚黏膜组织中定位的宿主细胞（如树突状细胞、巨噬细胞等）能够介导病毒向淋巴结的转运，在HIV-1初始感染中起到主导作用，提示这些免疫细胞在HIV-1感染中具有双刃剑作用。探讨宿主细胞介导的HIV-1传播感染，分析其在病毒建立初始感染中的作用，对于剖析HIV-1黏膜感染过程和寻找相应的抑制策略具有重要的意义。课题组以前的工作曾对树突状细胞介导HIV-1感染CD4+ T细胞（Trans-infection）的分子机制进行了系统的研究。本研究揭示亚黏膜组织中定位的肥大细胞同样可以捕捉HIV-1介导病毒感染T细胞。

肥大细胞主要分布于机体与外界环境接触的部位，如皮肤、消化道、肠道和生殖道黏膜等，是首先接触到病原体或过敏原的宿主细胞之一。肥大细胞最常见的报道是与哮喘、过敏等相关。肥大细胞可调节天然免疫和获得性免疫反应，近年来，其在抵御细菌、真菌、寄生虫和病毒等病原体入侵中的重要作用被逐渐重视。亚黏膜定位的肥大细胞与树突状细胞、巨噬细胞一样，是HIV-1黏膜侵染首先接触的宿主细胞。近期报道显示，肥大细胞在HIV-1感染妇女子宫颈组织中分布明显增加，提示肥大细胞在HIV-1感染中的可能作用。

博士研究生江爱平和研究助理蒋金凤等在王建华研究员的指导下，与南京医科大学附属江苏省人民医院、上海市第六人民医院、复旦大学附属上海市公共卫生临床中心，及美国Tulane灵长类研究中心等单位合作，从结肠癌旁组织黏膜中分离肥大细胞，分析其与HIV-1的相互作用。研究发现肥大细胞表达HIV-1受体或辅佐受体，可被HIV-1直接感染；更重要的是，发现肥大细胞表达C-型凝集素分子DC-SIGN、整合素α4β7及硫酸肝素等分子，作为HAF（ HIV attachment factor），能够结合HIV-1,然后把捕捉的感染性病毒颗粒传递给CD4+ T细胞，扩大HIV-1的传播感染。研究揭示了肥大细胞在HIV-1黏膜感染中的作用和分子机制，对于发展相应的HIV-1黏膜感染阻断策略具有重要的意义。

The gastrointestinal mucosa is the primary site at where HIV-1 invades, amplifies and becomes persistently established, and cell to cell transmission of HIV-1 infection plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and have been showed increased density in HIV-infected women genital mucosa. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic and bacterial infections. However the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs) DC-SIGN, HSPG, α4β7 integrin, and mediated capture of HIV-1 on the cell surface. Intriguingly, following co-cultured with CD4+ T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. The prior-blocking with anti-HAFs antibody or manan before co-culture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and were required for efficient cell to cell HIV-1 transmission. Our results revealed a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.