#When Chickenpox Turns Deadly

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WRITTEN BY: Kara Marker

In very rare cases – two in 10,000 people experts say – a chickenpox infection can trigger extremely dangerous brain inflammation. Until now, scientists didn’t know why this happened, and there was nothing they could do to predict or prevent it. Now, they’ve discovered a clue: a small mutation in the immune system’s DNA.
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Chicken pox caused by the varicella zoster virus. Credit: BruceBlaus
The problem isn’t necessarily a failed attack on the chickenpox virus; rather, it’s that the immune system never realizes that the virus is there at all. Varicella zoster virus (VZV), which causes chickenpox, can sneak in undetected on rare occasions when there is a mutation in the “POL III” sensor. The immune system relies on this sensor to ring the alarm when VZV makes its way into the body. Researchers discovered the role of POL III after mapping genomes of people who experienced these rare infections.

VZV is unique in that it only infects humans. It comes from the same family of viruses that cause herpes, and it often remains in the body after an initial infection, resurfacing years later causing shingles. In addition to causing brain inflammation in rare instances, VZV can also lead to severe pneumonia (twenty out of 10,000 people), which is especially dangerous for pregnant women.

A vaccine to prevent chickenpox entered the world in 1995, and the Centers for Disease Control and Prevention (CDC) reports that “each year, more than 3.5 million cases of varicella, 9,000 hospitalizations, and 100 deaths are prevented by varicella vaccination in the United States.”

“We cannot yet put an exact figure on how much the risk of complications is increased when you have this new immunodeficiency, since we have looked at relatively few patients in our study. Neither do we know how large a proportion of all those who have inflammation of the brain and pneumonia have the defect,” clarified Trine Hyrup Mogensen. “But we do know that this applies to both children and adults.”

Further analysis of the individual cells invaded by VZV confirmed that no immune response was initiated because the virus was never detected. But when researchers manually repaired the mutation, the immune system was suddenly aware of VZV, like taking off a blindfold.

Chickenpox isn’t the only infection that can enter the body undetected if there’s a specific mutation in the immune system’s DNA. Now that scientists know they can identify the genes responsible and even fix mutations to activate the immune system, this knowledge could spread to treat other diseases.

“We are now slowly becoming able to understand the individual differences in susceptibility to infections at both the genetic and molecular level,” said Soren Riis Paludan. He and the other researchers on the project see their study as a unique contribution to the advancement of personalized medicine, where treatments and diagnostics are based on individual cases and needs.

The present study was published in The Journal of Clinical Investigation.

Sources: Aarhus University, American Journal of Transplantation, CDC

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