JC Virus Carries a Mutation in MS Patients That Amplifies Brain Disease Known as PML

JC Virus Carries a Mutation in MS Patients That Amplifies Brain Disease Known as PML

A mutation in a mouse model of the John Cunningham (JC) virus, which causes progressive multifocal leukoencephalopathy (PML), allows the virus to evade the host immune responses in people with multiple sclerosis (MS), according to a study into the mechanisms of PML.

Infection with the JC virus most often passes unnoticed in healthy adults. For reasons still eluding scientists, however, MS patients treated with natalizumab (Tysabri), as well as patients with other autoimmune conditions and cancers treated with certain immunosuppressive drugs, are at increased risk of developing the brain disease.

“Nobody comes away unscathed from PML — you either die or you’re left with a lifelong searing neurological defect,” Aron E. Lukacher, chair and professor of microbiology and immunology at Penn State College of Medicine, said in a press release. “Because we don’t know how the drugs cause the JC virus to amplify from a silent infection, we really have no way of controlling it.”

Earlier research noted that JC virus isolated from patients with PML was mutated. The mutation, present as a change of a single amino acid, affects the part of the virus shell that allow it to dock into and infect human cells. Scientists demonstrated that the mutation alters the capacity of the virus to infect certain tissues, but until now they did not know whether it also had an impact on immune responses to the virus.

The study, Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner, published in the Journal of Virology, set out to explore this crucial question. Investigating mice with a mouse variant of the JC virus, the research team indeed found that when the mutation was present, immune T-cell responses were not as pronounced.

“We found that mouse polyomaviruses with a single amino acid change in their shell elicit a very different magnitude and quality of the T cell response that is needed to control the infection,” Dr. Lukacher said.

Researchers also found that the reduced T-cell activation was a result of altered type 1 interferon responses, immune factors normally activating T-cells.

“We need to find ways to improve the T cell responses in patients on these therapies,” concluded Dr. Lukacher.


  1. Steve Izard says:

    I have been taking infusions of Tysabri for the past 2 years, and stopped because of the risk increase of PML after 2 years. I am going to start taking oral medication Aubasio the first of June, following my final infusion of Tysabri on May 31st. I did research on all 3 of the oral medications for MS, and Aubasio was the only one that didn’t show cases of PML attributed to it. Do I have to be concerned with getting PML for the rest of my life?

  2. Bill C. says:

    “Earlier research noted that JC virus isolated from patients with PML was mutated.”
    I do not know the mechanism for transmitting the JC virus, but does this mean that the mutated form can be sent out into the general public due to MS (and other) treatments?

    • Audrey Mascarenhas says:

      My son aged 24 was diagnosed MS beginning this year and is taking TECFIDERA since March.
      He did a blood test initially to find out whether he carried the JC virus and it showed positive.
      I am very much concerned about he developing PML. iS IT ADVISABLE FOR HIM TO CHANGE TO AVONEX ?

      • Jamie Myers says:

        Yes, I was on Tecfidera and got off of it due to relapse and I had the test as well and tested positive because I was going to take tysabri but couldn’t

  3. Patricia Browne says:

    I took tysarbi for 2 years. It was during this time they first took blood and urine. I was positive for JV virus but my doctor felt it was still safe to stay with the infusions. I did for a little while but as the PML occurrences started to increase I went off the drug. Now years later I am at another ms center & they tested for JVC virus & the titer. I am positive & my titer is 3.75. Nobody really explains WHAT exactly it means. Does anyone do a study on patients who stopped the tysarbri & keep track of whether or not this virus can make me & others at risk for this virus to infect us?

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