The Aids virus has hideouts deep in the immune system that today's drugs cannot reach. Now scientists have finally 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
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.
A very smart virus
... 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.
"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.
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 their normal
"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 Rochester team found that HIV 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
That was good news, Kim said, 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.
Two drugs worked
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 evidence they show is in fact pretty good," said NIH's Jeang,
who says the next step should be a test of miltefosine in monkeys
infected with SIV, the monkey version of the Aids virus. – (Sapa-AP)