TUESDAY, April 29 (HealthDay News) -- Most drugs aimed at suppressing HIV target proteins lying on the virus itself, but new research suggests that focusing on the human host's immune cells might work even better.
That's because human cells mutate at much slower rates than does HIV, so the virus would have much less chance of mutating around the drug, scientists explained.
The research is still in its early stages, but it "provides a very nice model that you can inhibit a cellular protein and affect HIV replication," explained co-senior author Dr. Pamela Schwartzberg, a senior investigator at the U.S. National Human Genome Research Institute.
Her team published the findings in this week's edition of the Proceedings of the National Academy of Sciences.
Almost all antiretroviral drugs work by targeting a viral protein. But HIV replicates continually, raising the odds for drug-resistant mutations. For this reason, HIV-positive patients must often take two or three different medications, so that if one drug fails, the others will still fend off the virus.
But there's another player in HIV infection: the human immune system T-cell, the virus' preferred host. T-cells carry their own surface proteins, but because humans replicate much less often than HIV, the odds of developing drug-resistant genetic mutations are much lower.
"If you are looking to affect a human protein, it's going to be much less susceptible to the process of developing resistance," explained Rowena Johnston, vice president of research at The Foundation for AIDS Research (amfAR) in New York City.
In their research, Schwartzberg and co-senior author Andrew Henderson, of Boston University, decided to focus on a T-cell protein called interleukin-2-inducible T-cell kinase (ITK). ITK is a "signaling" protein that works in a variety of ways to activate T-cells.
An activated T-cell is the ideal host for HIV, Schwartzberg pointed out, and ITK appears to be crucial to HIV's invasion and spread.
"We found that there were several cellular processes in T-cells that HIV needs to use and that ITK was important to," she said. "In fact, it seems to affect three stages in the HIV life cycle. That was a real surprise to us."
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.