The AIDS virus has hideouts deep in the immune system that today’s drugs cannot reach. Now scientists finally have discovered how HIV builds one of those fortresses — and they are exploring whether a drug already used to fight a parasite in developing countries just might hold a key to break in.Researchers have long struggled unsuccessfully to attack what they call reservoirs of dormant HIV, and the new work is in very early stages.But University of Rochester scientists say it may be fairly straightforward to attack one of these reservoirs, blood cells called macrophages that HIV hijacks and turns into viral hideaways. The new discovery shows the exact steps that HIV takes to do that — and found that some existing drugs, including a long-used treatment for leishmaniasis called miltefosine, can block the main step and thus cause these cells to self-destruct.“It’s a very smart virus,” said lead researcher Dr Baek Kim. “They have to have a very good fence to protect their house for a long time. Get rid of the fence, and now their house is gone.”Today’s drugs have turned HIV from a quick death sentence into, for many, a chronic infection. Yet those drugs don’t eliminate HIV because they can’t reach the two known pools of cells where the virus can lie dormant, ever ready to resurface. So-called memory T-cells form one such pool. As the name implies, these are the cells that ensure if you get, say, measles as a child, you’re forever immune. They live for years, even decades, making them a logical HIV hideout, and one that scientists have repeatedly sought to dismantle to no avail.Macrophages, another type of immune cell, form the second pool. They roam the body looking for invaders like bacteria to gobble up. If they get harmed, such as becoming infected by a virus, they are supposed to commit suicide. But HIV instead keeps them alive long past normal lifespan.“Up to now, nobody has really thought about how to eliminate the macrophage reservoir,” said Dr. Kuan-Teh Jeang, an HIV specialist at the National Institutes of Health. “The imagination now has turned toward, ‘How do we eliminate reservoirs?’ The best way to address our problem is to simply kill those cells.” The virus produces a protein that turns on a particular cell-survival pathway. After a multistep process, it ultimately activates an enzyme called Akt that in turn prevents cell suicide, the researchers reported Thursday online in the journal Retrovirology.
