Promising HIV approach found
2008-04-30 08:10
Washington - Researchers have
pinpointed a protein in key human immune system cells needed
for the Aids virus to infect them, and found that turning it
off can greatly slow down the deadly virus.
Inactivating a protein called ITK in immune system cells
called T cells reduces HIV's ability to enter these cells and
replicate itself, the researchers said on Monday.
A drug based on this approach could be useful as a
complement to existing drugs used to treat HIV infection, said
Andrew Henderson of Boston University, one of the researchers.
It might also perhaps help battle problems with drug
resistance, added Dr Pamela Schwartzberg of the National Human
Genome Research Institute, part of the US National Institutes
of Health, another of the researchers.
Rapid mutation
"One of the real problems with treating HIV right now is
that most of the drugs that we have are directed against parts
of the virus," Schwartzberg said in a telephone interview.
"And with HIV, the virus rapidly mutates its genetic
material, its genome," added Schwartzberg, whose findings
appear in the journal Proceedings of the National Academy of
Sciences.
As a result, strains of the virus can emerge that are
resistant to drugs given to people to combat HIV infection.
Doctors have tried to battle the often-mutating virus by
giving people multi-drug regimens or switching drugs, but this
can elevate the risk of toxic side effects and be hard for
patients to follow.
As a result, researchers have considered taking aim at
proteins of human cells, which are much less apt to mutate.
Immune defence
Henderson's group interfered with interleukin-2-inducible T
cell kinase, or ITK, a protein that signals T cells to activate
against disease-causing invaders like viruses.
HIV ravages the body's immune system by attacking immune
system cells called T cells. HIV infects T cells and takes them
over to replicate - create more copies of itself.
Schwartzberg said ITK also is being examined as a possible
target for drugs to treat asthma or other ailments involving
the immune response. A member of his team of scientists
realized that the biological pathways the protein affected were
the same ones that are important to the Aids virus.
Working with human cells in a laboratory dish, the
researchers used two different methods separately to inactivate
ITK. One is a relatively new method called small interfering
RNAs or siRNAs, which can stop certain genes from functioning.
They also used a drug called BMS509744, which already had
been known to chemically interfere with the protein but had not
been looked at in the context of fighting HIV infection.
Both methods succeeded in undercutting HIV infection.
"We didn't completely block (infection) but we certainly
severely impaired it," Schwartzberg said. "It has minor effects
at multiple stages of HIV life cycle, and together that all
adds up to a more profound effect."
Schwartzberg said it could be years before any drug based
on the idea of inhibiting ITK could be tried in people, and
said more experiments are needed on human cells and HIV in the
lab assessing other ways of inhibiting the protein.
The NIH and the researchers have filed for a patent on the
idea of using ITK to treat HIV infection.