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New research showing how HIV targets
“veterans” or memory T-cells could change how drugs are used to stop the virus,
George Mason University researchers say. The research will appear in the
October edition of the Journal of Biological Chemistry and is currently
available online.
T-cells support the body's immune
system by organizing forces to fight off infection. Not all T-cells are the
same, however; some, experienced in fighting infection, are called memory
T-cells, and others, naive cells or "virgin" cells, haven't yet
encountered an infection. Mason researchers studied why HIV preferentially goes
after memory T-cells, while shunning naive T-cells, which appear similar.
“In the body, HIV is able to kill
most memory helper cells,” says Weifeng Wang, PhD, the study's main author. “We
wanted to pursue what makes the difference between memory and naive T-cells on
a molecular level.”
Unlike naive helper T-cells, memory
T-cells are on the go, and much more mobile. And it's that momentum that
attracts the virus and makes the memory cell vulnerable, says Wang, who's
currently a research fellow in the Dana-Farber Cancer Institute at Harvard
Medical School.
When a memory cell moves, inside the
cell, it looks like a waterfall on the moving edge. “It's called
'treadmilling',” says Yuntao Wu, an author of the study and professor at the
Mason-based National Center for Biodefense and Infectious Diseases. “The
cytoskeleton or the cell's supporting ‘bone’ is acting like a muscle. The
treadmilling of the cytoskeleton pushes the cell to migrate. That's how it
pushes itself. In the past year, we've been studying how HIV infects those
memory cells. It has to go to the center, into the nucleus. It has to go past
the cytoskeleton barriers to go into the center. For many years we didn't
understand how the virus could cross such a structure. It's like a wall. It has
to cross that wall.”
HIV jumps over the wall by exploiting
the cell's treadmilling process, Wu says. “The virus uses a receptor to attach
to the cell for entry,” he says. “When the virus touches that receptor it's
like someone ringing the doorbell. That triggers a signal—someone comes out and
opens the door. Now the HIV can start the treadmill to 'walk' along the
cytoskeleton towards the center. If the virus goes to naive cells, it cannot do
it. Naive cells aren't sensitive enough. The cytoskeleton of these 'virgin'
cells is different from the memory cells, and it is not easy for the virus to
start the treadmilling process.”
HIV's ability to mutate makes it
difficult for memory T-cells to recognize it. On top of that, the virus kills
many of the memory helper cells. By shifting the focus to the cell, away from
the virus itself, researchers may find a new way to tackle the virus, Wang
says.
“Basically, our new strategy will be
finding a cellular target, something HIV needs to depend on,” Wu says. “It's as
if the virus says 'give me a house.' The cell is the house. The house has to
have electricity and everything so it can live there. Our approach is to look
for something the virus needs to live in that house and then to reduce it or
shut it down. The challenge will be if you shut that down, that it doesn't impact
normal cell functions. It's a very tricky balance. You want to kill the virus
but not healthy cells along with it.”
Wu is looking at existing drugs,
including those used for cancer, due to the fact that cancer cells also
migrate. So some drugs that are used to slow down cancer migration could also
be used to treat HIV, Wu theorizes.
As part of his doctoral thesis, Wang
spent six years pursuing why HIV attacks memory cells. Failure is a part of
research, he says. Mentors and colleagues spurred Wang on. Sheer persistence
and hours in the lab eventually won out. “It's very challenging to do
scientific discovery,” Wang says. “There is no precedent.”
The Friends of AIDS Foundation is
dedicated to enhancing the quality of life for HIV positive individuals and
empowering people to make healthy choices to prevent the spread of the HIV
virus. To learn more about The Friends of AIDS Foundation, please visit: http://www.friendsofaids.org.
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