SAN FRANCISCO, May 22 -- A biochemical self-destruct trigger, a protein called RIPK3, found in many other types of cells appears to guard the lives of brain cells during infection with West Nile virus.
RIPK3 is better known for activating a certain type of cell death during infection or other 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.
In a recent Cell paper on how brain cells ward off West Nile virus, University of Washington (UW) researchers who led the research say the chemical pathway doesn't have to sacrifice brain cells to destroy the viruses and recruit the body's defenses against infection, and can preserve the brain's nerve cells, or neurons, by using an alternative approach to summon protection.
During a West Nile virus infection, the activation of RIPK3 in brain cells doesn't cause them to die. That is 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 and senior author on the paper.
RIPK3 responds to the presence of West Nile virus in the brain by placing an order for chemokines, the researchers observed.
The lead author of the paper, Brian Daniels, a UW Medicine postdoctoral fellow in immunology, explained that these chemicals underlie a successful ousting of West Nile virus. Chemokines attract an influx of infection-fighting white blood cells.
These efforts contribute to the clearance of the virus from the brain, but not by directly stopping replacement virus from reproducing within brain cells. Instead, the brain tissue undergoes a kind of inflammation that restricts the West Nile virus infection. "RIPK3 acts as part of the milieu of signals that support anti-viral inflammation in the brain," said Daniels.
In a different cell type, such as a fibroblast, the entry of a West Nile virus would result in the cell initiating its own demise.
