"Mice are very convenient, but they may not always recapitulate human diseases that well," Fuchs said. "Veterinary diseases happen naturally, and they provide a less convenient but a more truthful recapitulation of the human situation."
Interferon fights viruses by binding to an interferon receptor on cells, triggering a cascade of other molecular events and leading to the production of proteins that prevent viruses from reproducing or that stimulate other immune responses. But because too much interferon can harm the host's body, this signaling cascade has a built-in brake: Using a separate molecular pathway, interferon triggers the body's cells to remove its own receptor, so the immune system attack doesn't go on indefinitely.
"It's very important to understand what regulates the responsiveness of cells to interferon, and a major factor is the levels of cell-surface receptors," Fuchs said.
Although the researchers' investigations of these pathways led them to identify a target for improving the body's virus-fighting ability, they didn't set out to discover a drug. Rather, they were attempting to solve a paradox of cell biology.
The paradox rests on the fact that many steps in the interferon-signaling pathway involve adding a molecule of phosphate to proteins in the cascade. Interferon itself promotes the addition of phosphate onto the interferon receptor, yet previous evidence suggested that the receptor resisted being removed by the cell if it had phosphate added. Given that interferon does in fact trigger the removal of its own receptor, the research team hypothesized that an
|Contact: Katherine Unger Baillie|
University of Pennsylvania