Researchers have uncovered a new route for attacking HIV that may offer a way to circumvent problems with drug resistance.

In findings published April 28 in the online edition of the Proceedings of the National Academy of Sciences, researchers supported by the National Institutes of Health (NIH) report that they have blocked HIV infection in the test tube by inactivating a human protein expressed in key immune cells.

Most of the drugs now used to fight HIV, target the virus's own proteins.  HIV has a high rate of genetic mutation, however, and those viral targets change quickly. This leads to the emergence of drug-resistant viral strains, which can eventually prove fatal to long-term survivors of the virus who run out of drug options.

Doctors typically rely upon multi-drug regimens or switching drugs to outmaneuver the virus, but this is not always successful.

Research, like the one supported by the NIH, supports attacking HIV on a new front by developing drugs that target proteins of human cells, which are far less prone to mutations than viral proteins.

In the new study, researchers found that when they interfered with a human protein called interleukin-2-inducible T cell kinase (ITK) they inhibited HIV infection of 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.

"This new insight represents an important contribution to HIV research," said NHGRI Scientific Director Eric D. Green, M.D., Ph.D. "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."

When HIV enters the body, it infects T cells and takes over the activities of these white blood cells so that the virus can replicate. Eventually, HIV infection compromises the entire immune system and causes AIDS. The new work shows that without active ITK protein, HIV cannot effectively take advantage of many signaling pathways within T cells, which in turn slows or blocks the spread of the virus.

"We were pleased and excited to realize the outcome of our approach," 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."