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HIV is transmitted sexually, previous research has looked at biochemical measurements or morphology at various points during HIV transmission to investigate this process, researchers in France constructed an in vitro model of urethral mucosa in order to view it from the beginning to the end.
According to Morgane Bomsel, a molecular biologist at the Institut Cochin (INSERM, CNRS, Paris Descartes University), the precise sequence of events can be defined. 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 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. 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. The infected T cells seemed to target epithelial cells directly above macrophages. “The macrophage just stays still, ready to get the virus when it escapes the epithelial cells. But this dynamic observation allowed us to realize that the synapse is always formed on epithelial cells that are just above macrophages, suggesting we do have an interaction between the macrophages and the epithelium.
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. Once HIV is installed into a reservoir, it makes life very complicated if you want to eradicate the virus. Treatment with antiretroviral therapies can keep reservoirs of the virus latent, but stopping the therapy allows the virus to rebound and continue spreading.
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