Research in Action: PML Consortium Grant Seeks to Identify How JC Virus Causes Fatal Brain Disease

Richard Frisque, professor of molecular virology and the lead investigator on the grant, is studying the connections between immunomodulatory drugs and the development of JC virus-induced PML.

A two-year grant from the PML Consortium awarded to scientists in the Eberly College of Science aims to unravel sequence variations within the JC virus genome that could case the development of a rare fatal brain disease.

JC virus, or John Cunningham polyomavirus, infects between 50 and 70 percent of the human population, most often during early childhood or adolescence. Infections are usually asymptomatic, with most people unaware they have the virus unless their immune system is compromised by a disease or disease treatment.

In recent years, biopharmaceutical companies have developed a class of highly effective “miracle drugs” for debilitating conditions like multiple sclerosis, Crohn’s disease, and rheumatoid arthritis. Unfortunately, an unanticipated side effect of these drugs has been the reactivation of JC virus in the patient, resulting in the appearance of the rare, fatal brain disease progressive multifocal leukoencephalopathy (PML).

Richard Frisque, professor of molecular virology and the lead investigator on the grant, is studying the connections between these treatments and the development of JC virus-induced PML: “We are investigating why this one particular disease caused by this one particular virus is suddenly being activated in patients receiving therapies for unrelated illnesses.”

In collaboration with Vivek Nerurkar’s lab at the University of Hawaii, Frisque will use the $314,000 grant to investigate three forms of sequence variation identified in the JC virus genome, which are hypothesized to contribute to the pathogenic potential of this human virus. “Understanding the underlying mechanisms that lead a normally harmless virus to morph into an opportunistic pathogen capable of killing its host represents an initial step in combating PML.”

Frisque, Nerurkar, and their teams are assessing whether the loss of immune surveillance induced by this new generation of “miracle drugs” influences the genetic change responsible for PML’s devastating consequences.

For more information on research in the Department of Biochemistry and Molecular Biology, visit bmb.psu.edu.