Interactions of human microglia cells with Japanese encephalitis virus
Nils Lannes1, Viviane Neuhaus2, Brigitte Scolari2
1Department of Medicine, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland. nils.lannes@unifr.ch.
Background:
Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans. Severe Japanese encephalitis cases display strong inflammatory responses in the central nervous system and an accumulation of viral particles in specific brain regions. Microglia cells are the unique brain-resident immune cell population with potent migratory functions and have been proposed to act as a viral reservoir for JEV. Animal models suggest that the targeting of microglia by JEV is partially responsible for inflammatory reactions in the brain. Nevertheless, the interactions between human microglia and JEV are poorly documented.
Methods:
Using human primary microglia and a new model of human blood monocyte-derived microglia, the present study explores the interaction between human microglia and JEV as well as the role of these cells in viral transmission to susceptible cells. To achieve this work, vaccine-containing inactivated JEV and two live JEV strains were applied on human microglia.
Results:
Live JEV was non-cytopathogenic to human microglia but increased levels of CCL2, CXCL9 and CXCL10 in such cultures. Furthermore, human microglia up-regulated the expression of the fraktalkine receptor CX3CR1 upon exposure to both JEV vaccine and live JEV. Although JEV vaccine enhanced MHC class II on all microglia, live JEV enhanced MHC class II mainly on CX3CR1+ microglia cells. Importantly, human microglia supported JEV replication, but infectivity was only transmitted to neighbouring cells in a contact-dependent manner.
Conclusion:
Our findings suggest that human microglia may be a source of neuronal infection and sustain JEV brain pathogenesis.
Insights
Human microglia support Japanese encephalitis virus (JEV) replication and may transmit infection to neighboring cells, potentially sustaining JEV brain pathogenesis and neuroinflammation.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing severe neurological disease.
- Microglia, the brain's resident immune cells, are implicated as a viral reservoir for JEV.
- Interactions between human microglia and JEV remain poorly understood.
Purpose of the Study:
- To investigate the interaction between human microglia and JEV.
- To explore the role of human microglia in JEV transmission.
- To utilize primary human microglia and a novel monocyte-derived microglia model.
Main Methods:
- Exposure of human microglia to inactivated JEV vaccine and live JEV strains.
- Analysis of cytokine and chemokine production (CCL2, CXCL9, CXCL10).
- Assessment of CX3CR1 and MHC class II expression on microglia.
Main Results:
- Live JEV did not cause cell death but increased inflammatory mediators (CCL2, CXCL9, CXCL10).
- Human microglia upregulated CX3CR1 and, with live JEV, MHC class II on CX3CR1+ cells.
- Human microglia supported JEV replication, with contact-dependent transmission to adjacent cells.
Conclusions:
- Human microglia can support JEV replication.
- Human microglia may act as a reservoir for JEV, facilitating neuronal infection.
- These findings suggest a role for microglia in sustaining JEV pathogenesis in the brain.
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