科學家首次記錄下HIV通過性傳播的全過程

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.
雖然我們都知道性行爲是艾滋病病毒傳播的主要方式之一，但是我們卻對HIV是如何穿過生殖器粘膜，最終抵達免疫系統中的靶細胞知之甚少。

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.
在先前的研究中，科學家主要從生化指標或形態學的角度去研究HIV傳播的過程，但在發表在《細胞報告》期刊的一項研究中，來自法國的研究人員構建了體外尿道粘膜模型，來觀察整個傳播過程。

"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.
資深研究員、柯尚研究所的分子生物學家摩根·邦塞爾表示：“我們對關於HIV如何感染這種組織已經形成了一種全局觀點，但是通過實時可視化觀察對此進行追蹤是一種完全不同的方法。HIV傳播事件的精確發生順序就能夠被確定，我們對此感到非常吃驚。”

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.
在視頻中，被綠色熒光蛋白標記的HIV感染的T細胞，與重建的尿道黏膜組織上皮細胞相遇。當被感染的T細胞和上皮細胞接觸時，會形成一種在細胞表面突出的病毒學突觸結構。

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.
T細胞細胞膜的重排刺激了可感染的HIV的產生，後者在視頻中以綠色熒光點呈現。然後，就像科幻片裏衝擊槍發出的綠色熒光射線一樣，病毒顆粒在電光火石之間通過突觸穿過了黏膜上皮細胞。

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.
值得注意的是，在這一過程中上皮細胞並沒有被感染：病毒只是通過胞吞作用被裹在小泡裏穿過了細胞。而一旦它像這樣穿過了整個上皮細胞層，就會被基質中的巨噬細胞所捕獲。

After an hour or two, once the virus has been produced and shed, the cell contact ends and the infected T cell moves on.
一兩個小時後，一旦病毒產生和流出的過程結束，兩個細胞的接觸過程也結束，受感染的T細胞繼續運動，尋找下一個感染對象。

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.
這些被感染的T細胞存在於所有類型的生殖器官感染中。雖然遊離病毒可以在黏膜的細胞間隙中游走，但它們穿透粘膜的效率比細胞內的病毒低得多，後者可以利用病毒學突觸和胞吞作用穿越整個粘膜上皮細胞層。

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.
在接下來的20天裏，這些巨噬細胞會繼續產生並釋放病毒，隨後它們就進入了不產生病毒的潛伏狀態，但病毒依然儲存在這些巨噬細胞中。

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.
這爲艾滋病治療方案的研發帶來了新的挑戰：相比於已得到廣泛研究的、HIV潛伏在血液T細胞裏的過程，病毒經由生殖器粘膜進入巨噬細胞的過程的發生時間要早得多。

"Once HIV is installed into a reservoir, it makes life very complicated if you want to eradicate the virus," Bomsel says.
邦塞爾稱：“一旦病毒潛伏在免疫細胞中，想要根除就會讓情況變得非常複雜。”

Treatment with antiretroviral therapies can keep reservoirs of the virus latent, but stopping the therapy allows the virus to rebound and continue spreading.
雖然使用抗逆轉錄病毒療法可以使病毒保持潛伏狀態，但是一旦停止這種療法，病毒就會停止潛伏並繼續傳播。

"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."
“因此，我建議在感染病毒的早期就採取措施來避免病毒進入這種潛伏狀態，這也是爲什麼我認爲在粘膜上發揮作用的疫苗纔是患者真正需要的。因爲我們不能等。”

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."
這是她的研究團隊已經着手研究的課題。邦塞爾表示：“我們正在想辦法淨化那些儲存了病毒的細胞，因爲一旦能夠迫使病毒從這些細胞中出來，我們就能殺死它們。我們的另一部分工作是開發一種粘膜艾滋病毒疫苗。這是個非常複雜的研究領域，但我認爲它很重要。”