Around two-thirds of the world’s population carries human polyomavirus 2, one of a family of small DNA viruses that establish persistent, lifelong infections. Also called JC polyomavirus, it’s harmless and often undetected in healthy people.

But in immunocompromised people, JC polyomavirus can reactivate and spread to the brain. There, it infects and destroys specialized glial cells in the central nervous system that produce the myelin sheath. The resulting disease, progressive multifocal leukoencephalopathy, is often fatal, and has no cure.

This summer, an international research team reported how virus mutations can strategically interfere with how human antibodies recognize the virus, allowing it to evade an immune response. The new insights into the interactions between JC polyomavirus and the immune system, published in PNAS, could lay the foundation for the development of treatments and vaccines.

The research was led by scientists at the University of Tübingen in Germany, in collaboration with researchers from Brown and the University Hospital of Zürich in Switzerland.

“This work is the culmination of a 10-year international project between our institutions,” says Walter Atwood, PhD, the Viatris Professor of Biology and Medicine at Brown. “There’s now the possibility of therapeutic antibodies to be able to block an infection in patients who develop the disease. That’s been the thought and the goal, but getting to this point has been a significant challenge for a very long time.”

For the study, the research team drew on the observation that some patients are able to survive PML. “Their bodies manage to neutralize the attacking JC polyomaviruses so that they can no longer penetrate the body’s cells. The infection is stopped,” says study author Thilo Stehle, PhD, a professor at the University of Tübingen.

The immune system achieves this neutralization by producing precisely tailored antibodies, he says. The antibodies attach like a lock to binding sites on the viral capsid, which prevents the virus from binding to cells.

By studying the genetic mutations that can occur at the binding sites that antibodies use to defend themselves against the virus, the researchers found how the structure and mechanisms of action between JC polyomavirus and the human immune system could be used to develop therapeutics and vaccines.

Atwood’s lab showed that one of the antibodies protected cells against infection by both the JC polyomavirus as well as the related BK polyomavirus, which is also common in humans. While it does not cause brain disease, BK polyomavirus leads to nephropathy and hemorrhagic cystitis in kidney and bone marrow transplant patients, respectively.

“A potential vaccine could protect high-risk patients from infection with both polyomaviruses,” Atwood says.