The John Cunningham or JC virus is an extremely common and usually harmless virus. It occurs in between 7 and 9 out of every 10 people.

While the JC virus may not directly cause health problems and stays dormant in most people, it can lead to severe complications when it triggers a condition known as progressive multifocal leukoencephalopathy (PML).

People with multiple sclerosis (MS) might take medication that increases their risk of PML when they also have the JC virus.

In this article, we look at the JC virus, the dangers of PML, and the link between JC and MS. We also cover how doctors diagnose and treat PML.

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People who take immunosuppressant medications for MS, such as natalizumab, might experience complications from the otherwise harmless JC virus.

The JC virus occurs in the blood samples of 70 to 90 percent of people worldwide, and typically has no effect on its carriers.

Children with the JC virus often show no symptoms. The JC virus can also be present much later in life without complications.

The virus commonly occurs in the kidneys, bone marrow, gastrointestinal tract, and other body tissues.

According to an article in the World Journal of Neuroscience, the virus sits dormant in kidney tissue, and 40 to 75 percent of individuals eliminate the virus in their urine when they are around 30 years of age.

The JC virus typically causes no harm. However, some people with the virus face a high risk of developing PML, which is a potentially life-threatening condition.

In someone with PML, the protective coating of the nerve cells in the nervous system breaks down and damages the brain tissue.

The risk of PML increases in people with a suppressed immune system, such as people with an HIV infection or those receiving certain medications to treat autoimmune conditions that include MS.

If something reactivates the JC virus that is dormant in a person’s body, it can cause an infection that can lead to PML.

PML is incurable and can have severe physical effects. Complications include dementia, blindness, paralysis, and seizures.

For 30 to 50 percent of people who receive a PML diagnosis, the condition is fatal within the first few months of diagnosis.

According to an article in the World Journal of Neuroscience, PML has three stages:

  • Stage 1: Initial infection with the JC virus without symptoms
  • Stage 2: Inactive virus stays in the urinary tract, bone marrow, tonsils, lungs, spleen, and gut tissue
  • Stage 3: Active virus spreads toward the brain and central nervous system

Those at risk for developing PML include:

  • People with impaired immune systems due to HIV or treatment with certain medications.
  • People with autoimmune diseases, such as MS, whose treatment is with drugs that suppress the immune system.
  • People with certain types of cancer, such as lymphoma and leukemia.
  • People taking specific medications after an organ transplant.

Medicines that might lead to the development of PML in people with the JC virus include:

  • cyclophosphamide
  • corticosteroids
  • mycophenolate mofetil
  • monoclonal antibodies, such as natalizumab (Tysabri), rituximab (Mabthera), and alemtuzumab (MabCampath, Lemtrada)
  • other medications used to treat MS, such as dimethyl fumarate (Tecfidera), fingolimod (Gilenya), and ocrelizumab (Ocrevus)

The risk of the JC virus progressing to PML is higher for people with MS who take natalizumab.

A study published in the New England Journal of Medicine evaluated 19 people with MS who doctors were treating with natalizumab.

The researchers found an increase in levels of the JC virus in the participants’ urine after they started treatment with the drug. Urinary levels of the virus rose from 19 to 63 percent in the first 12 months of using natalizumab.

After a further 6 months, tests revealed that the virus had entered the blood cells of 60 percent of the study’s participants.

The researchers also found that the immune response to the JC virus was lower after 6 to 12 months of treatment with natalizumab.

They reported that among many of the people with MS taking the drug, the virus in their urine or blood samples had already undergone changes that contributed to its ability to reach the brain and cause PML.

None of the participants in the study, however, developed PML brain lesions.

Reactivation of the JC virus might cause cells to die. The virus may break down the protective coating of nerve cells, damaging the white matter of the brain.

PML is an aggressive, potentially fatal disease that infects the brain, and no cure is available at present. Its symptoms may onset rapidly and develop over a few weeks, or they may progress slowly, taking months.

Symptoms of PML can include:

  • clumsiness
  • increasing weakness
  • paralysis or lack of coordination
  • changes in vision, such as vision loss and blindness
  • speech impairments
  • personality and behavioral changes
  • seizures

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An MRI scan of the brain can identify PML.

A doctor can diagnose PML by several methods, including:

  • physical examination
  • MRI of the brain
  • examining the spinal fluid with a lumbar puncture to test for the JC virus

A negative spinal fluid test, which might occur in the early stages of the disease, cannot rule out a diagnosis of PML.

Another way to diagnose PML is by taking a brain biopsy and finding JC virus DNA or proteins. While this test might be the most reliable way to diagnose PML diagnosis, it is often too risky to perform.

The symptoms of a relapse of MS are similar to those of PML. People with MS should discuss their symptoms with a healthcare team for a thorough evaluation.

Once a doctor has diagnosed PML, treatment may include the use of plasma exchange to remove the medications causing the condition. Supportive care can also help.

However, there are no JC-virus-specific antiviral medications, and people with MS should discuss their risks for developing PML with their healthcare team.

In exceptional circumstances, the United States Food and Drug Administration (FDA) may permit doctors to use certain experimental medications.

At times, a condition called immune reconstitution inflammatory syndrome (IRIS) can occur. If this happens, drugs known as corticosteroids may help. However, people with compromised immune systems due to HIV cannot use these drugs.

The JC virus is common in many people, but more often than not remains dormant in the kidneys without causing any problems.

The link between the JC virus and MS is that some medications for MS suppress the immune system and activate the virus, leading to a potentially fatal condition called PML.

PML attacks nerve cells, breaking down their coating and causing them to die, damaging the white matter of the brain. However, PML is difficult to diagnose, and no treatment is currently available.


A person with MS, for whom I provide daily care, has received a PML diagnosis. What is the best way to make them comfortable?


The best treatment for a person with a new diagnosis of PML is to stop the medication that may be causing the PML. A blood treatment called plasma exchange can be used to remove the medication from the bloodstream when a doctor associates the PML with natalizumab.

Nancy Hammond, MD Answers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.