West Nile virus triggers brain inflammation by inhibiting protein degradation

January 23, 2020

West Nile virus (WNV) inhibits autophagy -- an essential system that digests or removes cellular constituents such as proteins -- to induce the aggregation of proteins in infected cells, triggering cell death and brain inflammation (encephalitis), according to Hokkaido University researchers. They also discovered that a drug can induce autophagy to remove protein aggregates and thus prevent cell death.

West Nile fever is a zoonosis spread by the bite of an infected mosquito. West Nile fever outbreaks have been reported across the world, mainly in North America and Europe, and caused hundreds of deaths in the past few decades. After a human becomes infected, virus replication temporarily occurs in peripheral tissues. In some patients, the virus enters the brain, infecting neural cells and causing cell death and serious cases of encephalitis.

The team previously found that WNV infection induces the accumulation of proteins in neural cells, but the detailed mechanisms underlying the accumulation and how it triggers neurological diseases remain unclear. There are also no established methods to specifically treat viral encephalitis, which can be caused by various types of viruses.

In the current study published in PLOS Pathogens, the research team including Shintaro Kobayashi and Kentaro Yoshii of Hokkaido University focused on autophagy to clarify how protein aggregates form in cells after WNV infection.

The researchers first identified the viral protein, called capsid protein, that induces accumulation of proteins in neural cells by having viral encoded-proteins expressed in cultured neural cells. The capsid protein induced accumulation and aggregation of proteins in the infected cells by inhibiting autophagy, a cellular digestive system. They also found that the capsid protein does so by disrupting an autophagy-inducing factor called AMP-activated protein kinase (AMPK). When they treated the infected cells with a drug that induces autophagy, protein aggregation and cell death were both suppressed.

Furthermore, a study using a mouse model demonstrated that WNV with mutations in the capsid protein was unable to harm neural cells or cause encephalitis. These findings suggest WNV inhibits autophagy through the capsid protein and the resulting accumulation of protein is involved in the onset of central nervous system disorders.

"Autophagy anomalies are involved in triggering various diseases, including neurodegenerative illnesses such as Alzheimer's disease. So, our finding could help elucidate the pathology of West Nile fever as well as various diseases associated with autophagy anomalies, and to develop treatment methods," said Shintaro Kobayashi of the research team at Hokkaido University.
-end-


Hokkaido University

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.