JC virus (Progressive multifocal leukoencephalopathy)

Definitions & Key takeaways

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the brain, caused by JC virus. JC virus is a non-enveloped, double-stranded DNA virus that can be found latent and harmless in most adults.

However, in people with weakened immune systems, the virus can cause PML, in which the white matter in the brain gets destroyed, leading to progressive and irreversible axon demyelination that presents with motor and cognitive neurological symptoms

There is no specific treatment for PML and it is usually fatal. However, some people with PML may improve with treatment for their underlying condition (e.g., HIV/AIDS).

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In progressive multifocal leukoencephalopathy, progressive means that the disease worsens over time, multifocal means the disease affects multiple locations, leuko refers to white, and encephalopathy refers to a disease of the brain.
So progressive multifocal leukoencephalopathy or simply PML, is a disease of the white matter of the brain that affects multiple locations and worsens over time.
If we look at a cross section of the brain, it can be divided into two areas: the outermost area is the grey matter, which is made up of neuron cell bodies, and the innermost area is the white matter, which is made up of the axons that come off of the neuron cell bodies.
The axons transmit electrical impulses to the next neuron in the series. The axons are surrounded by a fatty protective sheath called myelin that helps increase the speed at which electrical impulses are sent.
Myelin is produced by a special type of cells called oligodendrocytes. The cause of progressive multifocal leukoencephalopathy is the John Cunningham virus, or simply JC virus, named after the first patient in whom the virus was identified.
JC virus is a non-enveloped virus with closed circular double-stranded DNA genome. It’s thought that the virus is transmitted from person to person through the respiratory and gastrointestinal tract, and that it then moves through the bloodstream and eventually reaches kidney epithelial cells.
JC virus enters these kidney cells and starts replicating, but the cytotoxic CD8+ T cells of our immune system keep the virus in check by killing any cell that has replicating JV virus.
So to be clear, the virus is not eliminated, but instead it remains latent in the kidneys, meaning that it isn’t dividing and causing disease.
And It turns out that the vast majority of the population is infected by JC virus - that might include you! Most people with a healthy immune system are able to keep JC virus in the latent phase in the kidney epithelial cells for their entire life.
But things can change if the immune system gets weakened. This can happen for various reasons, like an HIV-infected individual who loses T cells, or individuals taking immunosuppressive medications like monoclonal antibodies such as natalizumab, which is typically used to treat multiple sclerosis, and rituximab, which is used to treat various cancers and autoimmune diseases.
All of these affect the lymphocytes, which are critical in helping to keep JC virus under control. Without them, the JC virus can start to get into the blood and make its way through the blood brain barrier and into the brain itself.
Within the brain, JC virus begins to rapidly attack oligodendrocytes in multiple locations throughout the brain causing demyelination of axons, and that interferes with communication between neurons, so messages start getting lost.
In progressive multifocal leukoencephalopathy, there can be a wide range of symptoms depending on where the demyelination occurs, including to progressive motor and cognitive neurologic symptoms like weakness, loss of vision, changes in speech, clumsiness due to lack of coordination, personality changes, and dementia.
The disease ultimately leads to death due to extensive brain damage in about half of the cases, and those who survive often retain serious neurological disabilities, since demyelination is irreversible.
Progressive multifocal leukoencephalopathy is usually suspected when an individual who’s recently become immunosuppressed develops new neurologic symptoms.
The diagnosis can be confirmed by finding JC virus DNA in the cerebrospinal fluid, as well as finding multiple white matter lesions on imaging techniques like brain MRI.
Generally, imaging techniques coupled to the clinical presentation are enough for diagnosis, and in rare cases, a brain biopsy can be performed on a living person, and that may show the presence of JC virus within oligodendrocytes.
There is no treatment for JC virus, but the disease can be slowed down by restoring the immune system, so that it can control the virus.
For example, HIV-infected people must start highly active antiretroviral therapy or HAART, while for autoimmune diseases, it’s helpful to stop immunosuppressive medications.
All right, as a quick recap, progressive multifocal leukoencephalopathy is a rare and often fatal demyelinating disease of the brain.
It is caused by a type of polyomavirus called JC virus, which specifically attacks oligodendrocytes, leading to progressive and irreversible axon demyelination that presents with motor and cognitive neurological symptoms.
JC virus can be found latent in most people, since a healthy immune system can keep it under control, but it can reactivate in case of immunosuppression, so the only way to treat progressive multifocal leukoencephalopathy is by restoring the immune system.