Scientists Study How HIV Hides in Body

By admin

Originally published on Advocate.com February 05 2008 1:00 AM ET

The AIDS virus
has hideouts deep in the immune system that today's drugs
can't reach. Now scientists finally have discovered how HIV
builds one of those fortresses -- and they're
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 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're supposed to commit suicide. But HIV
instead keeps them alive long past their normal life
span.

''Up to now,
nobody has really thought about how to eliminate the
macrophage reservoir,'' said 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 in the online version of the journal Retrovirology.

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.

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. (AP)