But would inhibiting ITK inhibit HIV? The researchers got help in answering that question from the pharmaceutical industry, which has been developing ITK inhibitor drugs as possible anti-asthma medications.
In laboratory experiments, Schwartzberg and Henderson used these experimental ITK inhibitors -- as well as another technique, called RNA interference -- to reduce ITK activity in HIV-infected T-cells.
"We could see rather dramatic effects on HIV replication in T-cells," Schwartzberg said.
Without active ITK in host T-cells, HIV found it much harder to enter the cell and to transcribe its genetic material into new viral particles, the team found. "The effect was quite strong over the course of a week, which was the length of time that we looked at," Schwartzberg said.
Of course, ITK is important to the proper function of immune T-cells, so questions remain as to whether its suppression might have unwanted side effects, such as a weakening of immune function. But experiments in mice suggest these effects might be minimal.
ITK-suppressed mice did have impaired immune function, but it was mostly confined to a specific type of response -- the defense the body mounts against allergies and asthma, Schwartzberg said. In other respects, ITK-suppressed cells appeared to "function in many circumstances, and they can fight off many infections," she noted.
Still, it's a long way from research in the test tube and in mice to human clinical trials. But the promise of a human cell-based HIV medication that attacks the virus at three different spots in its life cycle is hugely attractive, Johnston said.
"The virus would have to mutate in three different ways at once to overcome this ITK effect," she said. "It's not impossible, the virus can do it, but it would take a very long time."
Dampening down T-cell activity might not be such a bad idea, either, Johnston added, since HIV thrives on fully activated T-cells.
Schwartzberg said her team will continue to investigate the biological mechanisms underpinning the ITK-HIV relationship. In the meantime, she is optimistic that the drug industry will take up the gauntlet, in terms of clinical research.
"We hope that one of these companies that have developed ITK inhibitors will try and pursue this -- that would be wonderful," Schwartzberg said.
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