From: Reuters
Published April 28, 2008 05:44 PM

Study shows promising new approach to thwart HIV

By Will Dunham

WASHINGTON (Reuters) - Researchers have pinpointed a protein in a 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.

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It might also perhaps help battle problems with drug resistance, added Dr. Pamela Schwartzberg of the National Human Genome Research Institute, part of the U.S. National Institutes of Health, another of the researchers.

"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 DEFENSE

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.

(Editing by Maggie Fox)

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