PLoS patching: study reveals the mechanism of West Nile virus induced brain inflammation

January 26, 2020 / Biovalley / recently, researchers at Hokkaido University found that WNV inhibited autophagy to induce protein aggregation in infected cells, leading to cell death and brain inflammation (encephalitis) They also found that a drug can induce autophagy to remove protein aggregates, thereby preventing cell death West Nile virus infection is a zoonotic disease transmitted by mosquito bites that has killed hundreds of people in the past decades After infecting human, virus replication will happen temporarily in the surrounding tissues In some patients, the virus enters the brain, infects nerve cells and causes cell death and severe encephalitis The team has previously found that WNV infection can induce protein accumulation in nerve cells, but it is not clear how the basic mechanism of accumulation and how to trigger nervous system diseases, nor has a specific treatment for viral encephalitis been established In a recent study published in the journal PLO pathway, researchers at Hokkaido University revealed the effect of autophagy on protein aggregation in WNV infected cells The researchers first identified a viral protein called capsid protein, which induces protein accumulation in cultured neurons by expressing it in them Capsid proteins induce the accumulation and aggregation of proteins in infected cells by inhibiting autophagy They also found that capsid proteins are achieved by destroying autophagy inducing factors called amp activated protein kinase (AMPK) When they treated infected cells with autophagy inducing drugs, protein aggregation and cell death were inhibited In addition, studies using mouse models have shown that WNV with capsid mutations does not harm nerve cells or cause encephalitis These findings suggest that WNV inhibits autophagy through capsid protein, and the resulting protein accumulation is related to the onset of central nervous system disease Source of information: West Nile virus triggers brain information by inhibiting protein degradation original source: Shintaro Kobayashi et al, West Nile virus capped protein in hibits autophagy by amp activated protein kinase degradation in neurological disease development PLoS pathways (2020) Doi: 10.1371/journal.ppat.1008238