The West Nile virus causes inflammation of brain by inhibiting protein breakdown, West Nile virus (WNV) inhibits autophagy, an important system that absorbs or removes cellular components such as protein to induce protein aggregation in infected cells, which causes cell death and inflammation of the brain (encephalitis).
They also found that the drug could trigger autophagy to eliminate protein aggregates, thereby preventing cell death.
West Nile fever is a zoonotic disease transmitted by mosquito bites. Outbreaks of West Nile fever have been reported throughout the world, especially in North America and Europe, and have caused hundreds of deaths in the past few decades. After being infected, the virus replicates temporarily in peripheral tissue. the West Nile virus causes inflammation of brain by inhibiting protein breakdown.
In some patients, the virus enters the brain, infects nerve cells and causes cell death and severe cases of encephalitis.
The team previously found that WNV infection causes proteins to accumulate in nerve cells, but the exact mechanism underlying the accumulation and causes of neurological disorders is unclear.
There is also no established method for the specific treatment of viral encephalitis which can be caused by various types of viruses.
The researchers first identified a viral protein called capsid protein that induces the accumulation of proteins in nerve cells by expressing virus-encoded proteins in cultured nerve cells. Capsid proteins cause the accumulation and aggregation of proteins in infected cells by inhibiting autophagy, the cellular digestive system. They also found that capsid proteins do this by interfering with an autophagic inducing factor called AMP-Activated Protein Kinase (AMPK).
Protein aggregation and cell death are suppressed when treating infected cells with drugs that induce autophagy. In addition, a study using a mouse model showed that WNV with mutations in capsid proteins cannot damage nerve cells or cause encephalitis.
These results indicate that WNV inhibits autophagy through capsid proteins and that the accumulation of proteins produced is involved in the occurrence of central nervous system disorders.
Autophagic disorders have been implicated in triggering various diseases, including neurodegenerative diseases such as Alzheimer’s.
Researchers say: Our results can help clarify the pathology of West Nile fever, as well as various diseases associated with autophagic disorders, and develop treatments.