Expression profile of Japanese encephalitis virus induced neuroinflammation and its implication in disease severity - PubMed (original) (raw)

Expression profile of Japanese encephalitis virus induced neuroinflammation and its implication in disease severity

Nimesh Gupta et al. J Clin Virol. 2010 Sep.

Abstract

Background: Host immune response particularly through the induction of proinflammatory cytokines and chemokines in Japanese encephalitis virus infection has not been clearly understood in relation with pathogenicity and disease severity. The newly identified host mediators of pathogenesis could be the future target for diagnostic and therapeutics purpose.

Objectives: We investigated the mechanism of JE virus induced pathogenesis in terms of proinflammatory cytokine and chemokine secretion at molecular level in young one-week-old BALB/c mouse after subcutaneous administration of JEV.

Study design: Histopathology of brain was done to observe the morphological changes after JEV infection and genes relevant to macrophage activation, chemokine secretion, inflammatory cell infiltration, and blood-brain barrier permeability were examined at their gene and protein expression level for various time points after infection.

Results: At 6-day post-infection 100% mortality was observed. At 5-day post-infection, there was a robust expression of proinflammatory cytokines and chemokines with increased number of infiltrating inflammatory cells into the brain. Histopathology data confirms the infiltration of leucocytes and there was a marked upregulation in expression of genes relevant to infiltration. The expression pattern of macrophage receptor CLEC5A/DAP-12 signaling has shown the involvement in this robust neuroinflammation.

Conclusions: This is the first report that shows the involvement of monocyte and macrophage receptor CLEC5A in severe inflammatory response in JEV infection of brain. This study at gene expression level provides a hypothesis of neuroinflammation, a new lead in development of appropriate therapeutic, and prophylactics against Japanese encephalitis.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

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