Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
National HIV and Retrovirology Laboratory, JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, MB, Canada.
Front Immunol. 2019 Feb 6;10:144. doi: 10.3389/fimmu.2019.00144. eCollection 2019.
In the context of HIV sexual transmission at the genital mucosa, initial interactions between the virus and the mucosal immunity determine the outcome of the exposure. Hence, these interactions have been deeply explored in attempts to undercover potential targets for developing preventative strategies. The knowledge gained has led to propose a hypothetical model for mucosal HIV transmission. Subsequent research studies on this topic further revealed new mechanisms and identified new host-HIV interactions. This review aims at integrating these findings to inform better and update the current model of HIV transmission. At the earliest stage of virus exposure, the epithelial integrity and the presence of antiviral factors are critical in preventing viral entry to the submucosa. However, the virus has been shown to enter to the submucosa in the presence of physical abrasion or via epithelial transmigration using paracellular passage or transcytosis mechanisms. The efficiency of these processes is greater with cell-associated viral inoculums and can be influenced by the presence of viral and immune factors, and by the structure of the exposed epithelium. Once the virus reaches the submucosa, dendritic cells and fibroblasts, as recently described, have been shown of being capable of facilitating the transfer of viral particles to susceptible cells, leading to viral dissemination, most likely in a trans-infection manner. The presence of activated CD4 T cells in submucosa increases the probability of infection, where the predominant microbiota could be implicated through the modulation of an inflammatory microenvironment. Other factors such as genital fluids and hormones could also play an essential role in HIV transmission. Here, we review the most recent evidence described for mucosal HIV-transmission contributing with the understanding of this phenomenon.
在生殖器黏膜的 HIV 性传播中，病毒与黏膜免疫之间的初始相互作用决定了暴露的结果。因此，人们深入探索了这些相互作用，以期发现开发预防策略的潜在目标。这些研究获得的知识促使人们提出了一个关于黏膜 HIV 传播的假设模型。此后，针对该主题的进一步研究揭示了新的机制，并确定了新的宿主- HIV 相互作用。本综述旨在整合这些发现，以提供更好的信息并更新当前的 HIV 传播模型。在病毒暴露的最初阶段，上皮完整性和抗病毒因子的存在对于防止病毒进入黏膜下层至关重要。然而，已经表明病毒在存在物理磨损的情况下，或者通过上皮细胞旁渗透或转胞吞作用机制穿透上皮细胞进入黏膜下层。这些过程的效率在存在细胞相关病毒接种物时更高，并且可以受到病毒和免疫因子的存在以及暴露上皮的结构的影响。一旦病毒到达黏膜下层，最近描述的树突状细胞和成纤维细胞已被证明能够促进病毒颗粒向易感细胞的转移，从而导致病毒传播，很可能是以转染的方式。黏膜下层中激活的 CD4 T 细胞的存在增加了感染的可能性，其中定殖的主要微生物群可能通过调节炎症微环境而发挥作用。其他因素，如生殖液和激素，也可能在 HIV 传播中发挥重要作用。在这里，我们综述了描述黏膜 HIV 传播的最新证据，有助于理解这一现象。
