The research team at Hokkaido University has investigated the mechanism of infection in the case of the West Nile virus (WNV) – a virus with zoonotic potential. They found that this virus is capable of inhibiting autophagy that is a normal mechanism in the body to clear unhealthy and damaged cells, thus regenerating the newer and healthier ones.
By inhibiting this normal body mechanism for infected cells, the West Nile virus leads to aggregation of proteins, thus resulting in cellular death and inflammation in the brain (encephalitis). In addition to this, the research team also discovered that a drug that has the capability to stimulate autophagy can prevent cell death by clearing these aggregates of protein.
The bite of an infected mosquito can transmit this zoonotic illness – West Nile fever to healthy individuals. The disease outbreaks caused by the West Nile Virus have taken hundreds of lives in the last few decades and infected individuals throughout the world.
Mainly these disease outbreaks have been observed in Europe and North America. After a person gets infected by this virus, the virus replicates in peripheral tissues for a short period of time. While in some cases, the virus results in a serious infection by entering the brain.
After entering the brain, WNV starts infecting the cells there, resulting in cellular death and severe encephalitis (inflammation in the brain).
Previously, it was discovered that infection caused by WNV virus stimulates protein accumulation in the brain (neural) cells. But still, the researchers are uncertain about the detailed mechanisms that lead to this accumulation and how this process causes neurological disorders.
Up till now, there is no method that is recognized for particularly treating the cases of viral encephalitis that can be triggered by different viral strains.
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In the recent study, the researchers including Kentaro Yoshii and Shintaro Kobayashi at the Hokkaido University investigated the process of autophagy to have a clear understanding regarding how infection caused by West Nile virus leads to the formation of protein aggregates in the cells.
The findings of this research at Hokkaido University are presented in PLOS Pathogens. The expression of viral encoded-proteins in cultured brain cells has allowed the research team to discover a viral protein, known as the capsid, that stimulates protein accumulation in brain cells.
The capsid protein inhibits autophagy, forming proteins aggregates in the infected brain cells. This viral protein inhibits the process of autophagy by causing a disruption in AMP-activated protein kinase (AMPK) – a component that stimulates autophagy.
On further investigation, the research team observed suppression in both protein aggregation and cell death after the infected cells were exposed to a drug that can stimulate autophagy. Another study found that the West Nile virus with mutations in its capsid was unable to harm brain cells or trigger encephalitis.
Overall, these findings suggest that inhibition of autophagy by the West Nile virus and the subsequent protein accumulation are the underlying reasons for the onset of various CNS disorders.
These results can not only help in understanding the pathology of West Nile fever but also helps in understanding the underlying mechanism for various diseases caused by autophagy anomalies and in developing methods to treat these conditions.