Mapping the Measle Mutations That Helped It Spread in the Human Brain

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Mayo Clinic researchers have mapped how the measles virus mutated and spread in the brain of a person who died of a rare, fatal brain disease. New cases of this disease, which is a complication of the measles virus, may occur as measles re-emerges among the unvaccinated, researchers say.

Using the latest genetic sequencing tools, Mayo Clinic researchers have reconstructed how a collective of viral genomes colonized the human brain. The virus acquired a different mutation that led to the spread of the virus from the frontal cortex outward.

“Our study provides compelling data showing how viral RNA mutated and spread throughout the human organ, in this case the brain,” said Roberto Cattaneo, Ph.D., a Mayo Clinic virologist who is a co-lead author of a new PLOS Study of pathogens. “Our discoveries will help to study and understand how other viruses persist and adapt to the human brain, causing disease. This knowledge may facilitate the development of effective antiviral drugs.”

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What is measles?

Measles is one of the most contagious diseases. The measles virus infects the upper respiratory tract where it uses the trachea, or windpipe, as a trampoline to launch and spread through droplets that are scattered when an infected person coughs or sneezes.

Dr. Cattaneo led studies on how the measles virus spreads throughout the body.

He first began studying the measles virus about 40 years ago and was fascinated by a rare, fatal brain disease called subacute sclerosing panencephalitis (SSPE), which occurs in about 1 in every 10,000 measles cases. It can take about five to 10 years after the initial infection for the measles virus to mutate and spread throughout the brain. Symptoms of this progressive neurological disease include memory loss, seizures and immobility. Studied by Dr. Cattaneo had SSPE for several years until the deadly disease almost disappeared because more people were vaccinated against measles.

However, measles returned due to vaccine reluctance and non-vaccination. During the COVID-19 pandemic, millions of children did not receive their measles vaccines, resulting in an estimated 18% increase in measles cases and a 43% increase in deaths from measles in 2021 compared to in 2022 worldwide, according to a recent Centers for Disease Control and Prevention (CDC) report.

“We suspect that cases of SSPE will also rise. This is sad because this terrible disease can be prevented by vaccination. But now we are in a position to study SSPE with modern, genetic sequencing technology and learn more about it,” said Iris Yousaf, co-lead author of the study and a fifth-year Ph.D. candidate at the Mayo Clinic Graduate School of Biomedical Sciences.

Dr. Cattaneo and Yousaf have a unique research opportunity through a collaboration with the CDC. They studied the brain of a person who contracted measles as a child and died of SSPE years later in adulthood. They examined 15 specimens from different brain regions and performed genetic sequencing on each region to piece together the puzzle of how the measles virus mutates and spreads.

The researchers discovered that, after the measles virus entered the brain, its genome, the complete set of genetic material for the virus, began to change in harmful ways. The genome is replicated, creating other genomes that are slightly different. Then, these genomes are copied again resulting in many genomes each of which is also slightly different. The virus does this many times, creating a population of diverse genomes.

“In this population, two specific genomes have a combination of characteristics that work together to promote the spread of the virus from the initial location of infection in the frontal cortex of the brain to colonize the entire organ,” said Dr. Cattaneo.

The next steps in this research are to understand how specific mutations favor the virus spreading in the brain. These studies will be done on cultured brain cells and clusters of brain-like cells called organoids. This knowledge may help to develop effective antiviral drugs to prevent the spread of the virus in the brain.

However, pharmacological intervention in advanced stages of the disease is difficult. Prevention of SSPE by measles vaccination remains the best approach.

Reference: Yousaf I, Hannon WW, Donohue RC, et al. Capturing brain tropism: The spatial dynamics and evolution of the measles virus collective infectious unit that drives lethal subacute sclerosing panencephalitis. Palacios G, ed. PLoS Pathog. 2023;19(12):e1011817. doi: 10.1371/journal.ppat.1011817

This article is reprinted from the following materials. Note: material may be edited for length and content. For more information, please contact the cited source.

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