Nav: Home

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:

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.
BRAIN Initiative tool may transform how scientists study brain structure and function
Researchers have developed a high-tech support system that can keep a large mammalian brain from rapidly decomposing in the hours after death, enabling study of certain molecular and cellular functions.
Wiring diagram of the brain provides a clearer picture of brain scan data
In a study published today in the journal BRAIN, neuroscientists led by Michael D.
Blue Brain Project releases first-ever digital 3D brain cell atlas
The Blue Brain Cell Atlas is like ''going from hand-drawn maps to Google Earth'' -- providing previously unavailable information on major cell types, numbers and positions in all 737 brain regions.
Landmark study reveals no benefit to costly and risky brain cooling after brain injury
A landmark study, led by Monash University researchers, has definitively found that the practice of cooling the body and brain in patients who have recently received a severe traumatic brain injury, has no impact on the patient's long-term outcome.
Brain cells called astrocytes have unexpected role in brain 'plasticity'
Researchers from the Salk Institute have shown that astrocytes -- long-overlooked supportive cells in the brain -- help to enable the brain's plasticity, a new role for astrocytes that was not previously known.
Largest brain study of 62,454 scans identifies drivers of brain aging
In the largest known brain imaging study, scientists from Amen Clinics (Costa Mesa, CA), Google, John's Hopkins University, University of California, Los Angeles and the University of California, San Francisco evaluated 62,454 brain SPECT (single photon emission computed tomography) scans of more than 30,000 individuals from 9 months old to 105 years of age to investigate factors that accelerate brain aging.
More Brain News and Brain Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.