For previously healthy children, brain infections are rare. But about one out of every 10,000 people who are exposed to common viruses like herpes simplex or influenza will develop a potentially deadly disease, encephalitis.
Researchers have identified mutations in a single gene that may explain what goes wrong in cases of encephalitis of the brain stem, the part of the brain that controls many basic functions including heart rate and breathing.
Researchers evaluated seven children from unrelated families who had been exposed to a common virus (herpes simplex virus 1, influenza virus, or norovirus) and developed a life-threatening or lethal infection of the brain stem. The scientists discovered mutations in a gene called DBR1, which is responsible for producing a protein that helps process the loops formed in RNA during a step called mRNA splicing. Without it, immunity to viruses is selectively impaired in the brain stem.
Authors show that DBR1 expression is ubiquitous, but strongest in the spinal cord and brainstem. They also show that all DBR1 mutant alleles are severely hypomorphic, in terms of expression and function. The fibroblasts of DBR1-mutated patients contain higher RNA lariat levels than control cells, this difference becoming even more marked during HSV1 infection.
The experiments, published in Cell, point to an almost complete loss of DBR1 as the culprit, enabling brain stem virus invasion in all seven patients. Authors also show that the patients’ fibroblasts are highly susceptible to HSV1. RNA lariat accumulation and viral susceptibility are rescued by wild-type DBR1. The findings also reveal an unexpected connection between an RNA processing mechanism and protective immunity in a specific region of the brain.
https://www.rockefeller.edu/news/21415-mutation-explains-people-vulnerable-viral-brain-infection/
http://www.cell.com/cell/fulltext/S0092-8674(18)30163-6
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