A genetic modification in the ‘coat’ of a brain infection-causing virus may allow it to escape antibodies, according to Penn State College of Medicine researchers. They say testing people for this and other viral mutations may help identify patients at risk for developing a fatal brain disease.

Dr. Aron Lukacher, professor and chair of the Department of Microbiology and Immunology at the College of Medicine, and Susan Hafenstein, professor of medicine and microbiology and immunology at the College of Medicine and professor of biochemistry and molecular biology at Penn State Eberly College of Science, co-led a research team that used high-resolution microscopy to study the capsid, or outer shell of mouse polyomavirus (MuPyV). This virus is a genetic model of JC polyomavirus (JCPyV), which is present and harmless in most people and can cause progressive multifocal leukoencephalopathy (PML), a brain disease, in people taking immunosuppressive therapies.

Genetic mutations in the capsid of JCPyV are common in PML patients and scientists have struggled to understand whether they allow the virus to infect brain cells or whether the resulting changes allow the virus to evade elimination by antiviral antibodies and then cause brain infection. Lukacher and Hafenstein studied the mouse equivalent of a common genetic mutation in JC polyomavirus to try and better understand how it may cause PML.

“Not much is known about how this particular genetic mutation in the JC polyomavirus capsid leads to PML,” Lukacher said. “It has been detected in the blood, cerebrospinal fluid and brain tissues of PML patients but not in their urine. This unmutated virus typically sits dormant in the kidneys of healthy people, which got us wondering how this particular mutation contributes to disease progression.”

The researchers introduced a genetic mutation in the MuPyV capsid similar to one found in JCPyV and conducted a series of experiments to compare outcomes between MuPyV and the altered virus. The virus mutates by swapping out one amino acid, the chemical ingredients used to build the capsid, for another. They found the virus was still able to cause central nervous system infection and hydrocephalus, or brain swelling.

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