艾滋病是如何通过性行为传染的？

While it’s well known that HIV is transmitted sexually, how the virus crosses genital mucus membranes to reach its targets in the immune system is less well understood. Previous research has looked at biochemical measurements or morphology at various points during HIV transmission to investigate this process, but in a study published in the journal Cell Reports, researchers in France constructed an in vitro model of urethral mucosa in order to view it from start to finish.

众所周知，性行为是艾滋病病毒传播的主要方式之一。但是，HIV是如何穿过生殖器粘膜，最终抵达免疫系统中的靶细胞的？我们却知之甚少。在先前的研究中，科学家主要从生化指标或形态学的角度去研究HIV传播的过程。在《细胞.报告》（Cell Reports）杂志最新发表的一项研究中，来自法国的研究人员在他们构建了体外尿道粘膜模型HIV在性行为中的开始和结束的传播过程。

We had this global idea of how HIV infects this tissue, but following something live is completely different. The precise sequence of events can be defined, and we were very surprised by them, says senior researcher Morgane Bomsel, a molecular biologist at the Institut Cochin (INSERM, CNRS, Paris Descartes University).

“我们对HIV侵入人体组织的过程有着宏观的认识，但直接追踪活体组织中真实发生的情况是与前者完全不同的。令人惊喜的是，这项技术使得我们对整个过程中的每一步都有清晰的认识，”这篇论文的主要作者，巴黎第五大学的分子生物学家Morgane Bomsel说。

In the videos, a T cell infected with fluorescent-green-labeled HIV encounters epithelial cells of a reconstructed urethral mucosal tissue. When the infected T cell and an epithelial cell come into contact, a kind of pocket forms, called a virological synapse. This rearrangement of the infected cell’s membrane spurs production of infectious HIV virus, which appears in the videos as green fluorescent dots. Then, like the neon green ray of a blaster gun in an old sci-fi movie, the virus sheds across the synapse into the mucosal epithelial cell. Importantly, the epithelial cell isn’t infected: the virus simply travels across the cell via transcytosis. Once it crosses the epithelial layer, it’s captured by immune cells called macrophages in the stroma. After an hour or two, once the virus has been produced and shed, the cell contact ends and the infected T cell moves on.

在视频中，被绿色荧光蛋白标记的HIV感染的T细胞，与重建的尿道黏膜组织上皮细胞（蓝色）相遇。当被感染的T细胞和上皮细胞接触时，会形成一种在细胞表面突出的病毒学突触（virological synapse）结构。T细胞细胞膜的重排刺激了可感染的HIV的产生，后者在视频中以绿色荧光点呈现。然后，就像科幻片里冲击枪发出的绿色荧光射线一样，病毒颗粒在电光火石之间通过突触穿过了黏膜上皮细胞。值得注意的是，在这一过程中上皮细胞并没有被感染：病毒只是通过胞吞作用被裹在小泡里穿过了细胞。而一旦它像这样穿过了整个上皮细胞层，就会被基质中的巨噬细胞所捕获。一两个小时后，一旦病毒产生和流出的过程结束，两个细胞的接触过程也结束，受感染的T细胞继续运动，寻找下一个感染对象。

These infected T cells are present in all genital fluids that vector infection. While cell-free viruses can cross the mucosa, they are much less efficient at penetrating it than cell-bound viruses that can make use of the virological synapse and transcytosis.

这些被感染的T细胞存在于所有类型的生殖器官感染中。虽然游离病毒可以在黏膜的细胞间隙中游走，但它们穿透粘膜的效率比细胞内的病毒低得多，后者可以利用病毒学突触和胞吞作用穿越整个粘膜上皮细胞层。

These macrophages continue to produce and shed the virus for 20 days, after which they enter a latent, non-virus-producing state. But the virus is still stored in the macrophage. This poses a challenge for efforts to develop treatments for HIV, because the virus reaches these macrophage reservoirs in the genital tissue much earlier in the infection process than more frequently studied T cell reservoirs in the blood.

在接下来的20天里，这些巨噬细胞会继续产生并释放病毒，随后它们就进入了不产生病毒的潜伏状态，但病毒依然储存在这些巨噬细胞中。这为艾滋病治疗方案的研发带来了新的挑战：相比于已得到广泛研究的、HIV潜伏在血液T细胞里的过程，病毒经由生殖器粘膜进入巨噬细胞的过程的发生时间要早得多。

Once HIV is installed into a reservoir, it makes life very complicated if you want to eradicate the virus, Bomsel says. Treatment with antiretroviral therapies can keep reservoirs of the virus latent, but stopping the therapy allows the virus to rebound and continue spreading. "So an aim would be to act extremely early upon infection to avoid this reservoir formation, which is why I think a vaccine active at the mucosa is what you would need. Because you can’t wait."

“一旦病毒潜伏在免疫细胞中，想要根除就会让情况变得非常复杂，”Bomsel说。虽然使用抗逆转录病毒疗法可以使病毒保持潜伏状态，但是一旦停止这种疗法，病毒就会停止潜伏并继续传播，“因此，我建议在感染病毒的早期就采取措施来避免病毒进入这种潜伏状态，这也是为什么我认为在粘膜上发挥作用的疫苗才是患者真正需要的。因为我们不能等。”

This is something her team is already at work on. "We are trying to find ways to purge the reservoir, because we think we know how to kill the virus once we shock the reservoir. And another part of what we do here is work to develop a mucosal HIV vaccine," she says. "It’s a complicated field, but I think it’s important."

这是她的研究团队已经着手研究的课题。“我们正在想办法净化那些储存了病毒的细胞，因为一旦能够迫使病毒从这些细胞中出来，我们就能杀死它们。我们的另一部分工作是开发一种粘膜艾滋病毒疫苗，”她说。“这是个非常复杂的研究领域，但我认为它很重要。”