JC virus (Progressive multifocal leukoencephalopathy)


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JC virus (Progressive multifocal leukoencephalopathy)


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JC virus (Progressive multifocal leukoencephalopathy)


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USMLE® Step 1 questions

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JC virus (Progressive multifocal leukoencephalopathy)

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USMLE® Step 1 style questions USMLE

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A patient presents to a local clinic complaining of unilateral weakness on the right side and diplopia. He has a history of AIDS, with a recent CD4+ T cell count of 52 cells/microL. MRI of the head shows multifocal white matter lesions.  Cerebrospinal fluid PCR is positive for a non-enveloped, double-stranded DNA virus. Which of the following is the most likely cause of this patient’s presentation?  

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Progressive multifocal leukoencephalopathy (PML) p. 509, 542

HIV-positive adults p. 174

polyomaviruses p. 161

rituximab p. 449



Antonella Melani, MD

Gil McIntire

Tanner Marshall, MS

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.


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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