Researchers from the Mayo Clinic and elsewhere have mapped how the measles virus mutated and spread in the brain of an individual who died from a rare brain disease called subacute sclerosing panencephalitis (SSPE). Details of the findings were published this week in PLOS Pathogens in an article titled “Brain tropism acquisition: the spatial dynamics and evolution of a measles virus collective infectious unit that drove lethal subacute sclerosing panencephalitis.”
Measles cases have dwindled thanks to effective vaccinations against the disease. However infection rates have begun climbing due to factors like vaccine hesitancy and missed vaccinations. The Centers for Disease Control and Prevention (CDC) estimates that millions of children missed their measles vaccinations during the COVID-19 pandemic, resulting in about an 18% increase in infections.
In roughly one out of every 10,000 measles cases, the patients go on to develop SSPE. It can take five to ten years from initial infection for the measles virus to mutate and spread throughout the brain. When it does so, patients experience symptoms such as memory loss, seizures, and immobility. With the numbers of unvaccinated people rising and the uptick in measles infections, it is possible that cases of SSPE may begin to rise as well.
Working alongside their collaborators at the CDC and elsewhere, the Mayo scientists studied the autopsied brain of a 24-year old male who was infected with measles as a child and then developed SSPE as an adult. They collected and deeply sequenced viral RNA from 15 specimens from different regions of the patient’s brain to figure out how the measles virus mutated and spread.
Their analysis showed that the virus replicated in the brain, creating multiple genomes that were slightly different from each other. Each individual genome replicated resulting in a population of varied viral genomes in the brain. Within that population, the researchers identified two specific genomes accumulated mutations that had the right blend of characteristics needed to promote the spread of the virus from the frontal cortex where the migration began on to the rest of the brain. In fact, “most infected cells carried both genome types, suggesting the possibility of genetic complementation,” they wrote.
While this study focused on measles, the scientists envision broader implications for their work. “Our study provides compelling data that shows how viral RNA mutated and spread throughout a human organ—the brain, in this case,” said Roberto Cattaneo, PhD, a Mayo Clinic virologist and co-lead author on the study. “Our discoveries will help [with] studying and understanding how other viruses persist and adapt to the human brain, causing disease.” Their findings could also “facilitate the generation of effective antiviral drugs,” he added.
For their next steps, the scientists plan to study exactly how specific genomic mutations identified enable the virus to spread in the brain. They’ll use cultivated brain cells as well as brain organoids for these studies.
