Impaired Autophagy Flux is Associated with Proinflammatory Microglia Activation Following Japanese Encephalitis Virus...

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• The role of autophagy in Japanese encephalitis virus (JEV) infection remains largely unexplored.
• Understanding cellular mechanisms is crucial for JEV pathogenesis.

Purpose of the Study:

• To investigate the role of autophagy flux in microglia activation, neuroinflammation, and neuronal death during JEV infection.
• To elucidate the impact of JEV on autophagy pathways and neuronal integrity.

Main Methods:

• Utilized a mouse model of JEV infection.
• Analyzed autophagy markers (LC3-II/I, SQSTM1/P62), neuronal death markers (caspase 12, H2Ax), and cathepsin D activity.
• Assessed microglia activation, pro-inflammatory cytokines (IL1β, TNF-α, IFNγ, IL6), and neurobehavioral function.
• Employed BV2-microglia and N2a-neuronal cell lines for in vitro studies.

Main Results:

• JEV infection led to increased autophagy markers (LC3-II/I, SQSTM1/P62) and decreased cathepsin D activity by day 7.
• Activated microglia exhibited elevated pro-inflammatory cytokine expression and increased DNA damage (H2AX) and neuronal cell death.
• Neurobehavioral dysfunction and neuronal cell death pathways were observed in the hippocampus.
• Inhibition of autophagy flux and neuronal cell death were consistent in N2a neuronal cells post-JEV infection.

Conclusions:

• JEV infection disrupts autophagy flux, contributing to microglial activation and neuroinflammation.
• Autophagy dysregulation plays a significant role in JEV-mediated neurodegeneration.
• Findings highlight autophagy modulation as a potential therapeutic target for JEV infection.