Human immune cell protein opens new front in fighting AIDS virus

Washington, Apr 29 : A research group supported by the US' National Institutes of Health (NIH) has blocked HIV infection in the test tube by inactivating a human protein expressed in key immune cells - a process that may offer a way to circumvent problems with drug resistance.

In the new study, Pamela Schwartzberg, M.D., Ph.D., a senior investigator at the National Human Genome Research Institute (NHGRI), part of NIH; Andrew J. Henderson, Ph.D., of Boston University; and their colleagues used a chemical inhibitor and a type of genetic inhibitor, called RNA interference, to inactivate a human protein called interleukin-2-inducible T cell kinase (ITK) in key human immune cells called T cells.

ITK is a signaling protein that activates T cells as part of the body's healthy immune response.

Then, the T cells were exposed to HIV, and the researchers studied the effects of ITK inactivation upon various stages of HIV's infection and replication cycle.

Suppression of ITK reduced HIV's ability to enter T cells and have its genetic material transcribed into new virus particles.

However, ITK suppression did not interfere significantly with T cells' normal ability to survive, and mice deficient in ITK were able to ward off other types of viral infection, although antiviral responses were delayed.

Dr. Schwartzberg said: "Suppression of the ITK protein caused many of the pathways that HIV uses to be less active, thereby inhibiting or slowing HIV replication."

Current drugs used to fight HIV target the virus's own proteins. However, because HIV has a high rate of genetic mutation, those viral targets change quickly and lead to the emergence of drug-resistant viral strains.

"Finding a cellular target that can be inhibited so as to block HIV validates a novel concept and is an exciting model for deriving potential new HIV therapies," said NHGRI Scientific Director Eric D. Green, M.D., Ph.D..

In findings are published in the online edition of the Proceedings of the National Academy of Sciences.

ANI