JC Polyomavirus: Deadly but with a weakness for sugar

It doesn’t strike often but when the JC polyomavirus does, it’s ruthless. The virus preys on people with weakened immune systems and almost always kills them.
Now the killer may have a target on its back. An international team has uncovered that the virus must bind to a very specific sugar molecule dangling from the side of the brain cells it attacks.

The finding, reported this week in the journal Cell Host & Microbe, could provide a basis for developing drugs to interrupt that process.

Researchers from Brown University, the University of Tübingen in Germany, and Imperial College in London painstakingly characterized the precise structure and biology of how the virus binds to host cells down to the atomic level.

By exposing a specific target, the work sets the table for drug development to begin, says Walter Atwood, professor of molecular biology, cell biology, and biochemistry at Brown and a senior author of the study.

“The overall goal is to get these ‘plans’ and then design small molecules—drugs that will fit in this receptor, binding and preventing infection,” Atwood says.

Atwood notes that this paper also marks the first time anyone has fully determined the structure and binding functionality of a human polyomavirus. While the JC polyomavirus causes the brain-wasting disease known as PML, others in the “family” are implicated in ailments such as skin cancers.

When the virus floats toward a cell, it encounters a metaphorical cityscape of sugary molecules on its surface, says Brown postdoctoral researcher Melissa Maginnis, one of the paper’s two lead authors. The team wanted to know which one the virus chooses.