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A comparative medicine study by Penn vet identifies a new approach to combat viral infections
Date:11/9/2012

other enzyme must be at work in the pathway to remove the phosphate molecule from the receptor so it could be consumed by the body's cells to ramp down the immune-system response to viruses.

Performing a screening for this putative enzyme, they identified protein tyrosine phosphatase 1 B (PTP1B) as a likely candidate. In a series of experiments, the researchers confirmed that blocking PTP1B decreased the removal of the interferon receptor. As a result, interferon signaling became enhanced. Using human cells infected with hepatitis C, the researchers found that adding a PTP1B inhibitor allowed smaller doses of interferon to be effective in keeping the virus from reproducing. They demonstrated a similar effect in human cells infected with vesicular stomatitis virus.

Aiding in their work was the fact that pharmaceutical companies have already designed multiple drugs that inhibit the activity of PTP1B but for a completely separate reason than the enzyme's involvement in interferon signaling.

"PTP1B also works on the leptin receptor," Fuchs said. "This is the pathway that regulates satiety, appetite and weight gain. So in the past 10 years there have been massive industrial and academic undertaking to develop PTP1B inhibitors to treat obesity and diabetes."

To see how these PTP1B inhibitors would impact viral infections in a living organism, the researchers could not use mice because mice lack a portion of the receptor that PTP1B acts upon, and so blocking PTP1B does not impact interferon signaling in the same way as it does in humans and other mammals. Instead, they examined five cats that had been enrolled by their owners in the study. Each was suffering from chronic stomatitis, a condition that involves substantial inflammation in the mouth and makes it painful for the cats to eat and groom. The cats received a single injection of a PTP1B inhibitor. Two weeks later, all five showed noticeable reductions in redness and inflammation
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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert

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