Scientists claim to have uncovered a new route for attacking HIV -- they have blocked the viral infection in test tube by activating a human protein expressed in key immune cells.
Most of the drugs now used to fight HIV, which is the retrovirus that causes AIDS, target the virus' own proteins. But those viral targets change quickly and lead to emergence of drug-resistant viral strains.
But the scientists 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 activates T cells as part of the body's healthy immune response.
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.
But, according to the scientists, the new work shows that without active ITK protein, HIV cannot effectively take advantage of many signalling pathways within T cells, which in turn slows or blocks the spread of the virus.
"We were pleased and excited to realise the outcome of our approach. Suppression of the ITK protein caused many of the pathways that HIV uses to be less active, inhibiting or slowing HIV replication," said lead researcher Pamela Schwartzberg.
In their lab experiment, Schwartzberg of the US-based National Human Research Genome Institute and colleagues from Boston University used a chemical inhibitor and a type of genetic inhibitor, called RNA interference, to inactivate ITK in human T cells.
Subsequently, the T cells were exposed to HIV, and the researchers studied the effects of ITK inactivation on 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.
"ITK turns out to be a great target to examine," Schwartzberg said.
Added NHGRI Scientific Director Eric D. Green: "This insight represents an important contribution to HIV research. Finding a cellular target that can actually be inhibited so as to block HIV validates a novel concept and is an exciting model for deriving new HIV therapies."
The results of the study have been published in the latest edition of the Proceedings of the National Academy of Sciences journal.
