Scientists study how HIV hides in body (AP)
Posted by admin on Jan 31, 2008
Researchers have long struggled unsuccessfully to attack what they appoint 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 end that — and found that some existing drugs, including a long-used treatment for leishmaniasis called miltefosine, be able to block the main step and thus inducement 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 far-seeing time. … Get rid of the fence, and now their house is gone.”
Today’s drugs have turned HIV from a quick death judicial decree 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 be able to lie dormant, ever quick to resurface.
So-called memory T cells form one such pool. As the name implies, these are the cells that ensure suppose that you get, say, measles as a child, you’re forever immune. They live for years, even decades, making them a consistent HIV hideout, and one that scientists have repeatedly sought to dismantle to no be of advantage.
Macrophages, not the same type of immune cell, form the second pool. They roam the body looking for invaders analogous bacteria to gobble up. grant that they get harmed, such as becoming infected by a virus, they’re supposed to commit suicide. But HIV instead keeps them alive long past their normal lifespan.
“Up to now, nobody has really thought about how to eliminate the macrophage receptacle,” said Dr. Kuan-Teh Jeang, an HIV specialist at the National Institutes of Health. “The imagination now has turned toward, ‘How accomplish we eliminate reservoirs?’ … The best practice to address our problem is to simply kill those cells.”
The Rochester team found that HIV produces a protein that turns onward 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.
That was good news, Kim related, because the Akt pathway is a culprit in certain cancers — meaning oncologists have been trying to target it for some time. So Kim put human HIV-infected macrophages in lab dishes and started adding drugs known to block the Akt pathway, to see if any killed the cells.
He had luck: Miltefosine and a cousin named perifosine both rapidly killed the macrophages, thus depriving HIV of this hideout.
Perifosine is currently being studied as a possible cancer drug. But miltefosine is known to be safe through its use in leishmaniasis patients. So Kim’s goal is to rapidly study the already available miltefosine in animals, to see if it truly targets infected macrophages well enough to then test in HIV patients.
“The evince they representation is in fact tolerably good,” said NIH’s Jeang, who says the next step should be a test of miltefosine in monkeys infected by SIV, the monkey interpretation of the AIDS poison.