Brain Fights West Nile Virus in Unexpected Way
In a turnabout, a biochemical self-destruct trigger found in many other types of cells appears to guard the lives of brain cells during an infection with West Nile virus.
UW Medicine scientists led research showing that this chemical pathway doesn’t have to sacrifice brain cells to destroy the viruses and recruit the body’s defenses against infection.
The self-destruct trigger, a protein called RIPK3 (pronounced rip-3), is better known for activating a certain type of cell death during infection or damaging events in other parts of the body. The death of infected cells in this manner is a protective mechanism that helps the body eliminate the infection.
During a West Nile virus infection, however, the activation of RIPK3 in brain cells doesn’t cause them to die. That’s because its signaling within the central nervous system is not the same as in cell types elsewhere in the body. Its brain-specific role implies that there are central nervous system functions for RIPK3 not observed in other tissues.
“There is something special about neurons, perhaps because they are non-renewable and too important to undergo cell death,” said Andrew Oberst, assistant professor of immunology at the University of Washington School of Medicine. He is the senior author of a recent Cell paper on how brain cells ward off West Nile virus.
“RIPK3 acts as part of the milieu of signals that support anti-viral inflammation in the brain,” said the lead author of the paper, Brian Daniels, a UW Medicine postdoctoral fellow in immunology.
RIPK3 responds to the presence of West Nile virus in the brain by placing an order for chemokines, the researchers observed.
Daniels explained that these chemicals underlie a successful ousting of West Nile virus. Chemokines attract an influx of infection-fighting white blood cells.