Comprehensive Assessment of Human Cerebrospinal Fluid for Protein Bio-Marker Identification Following Japanese Encephalitis Viral Infection

Abstract

Identifying potential biomarkers, which can be used for diagnostic and therapeutic purposes, is urgently needed for successful Japanese encephalitis (J.E.) viral infection disease management. In the present study, we identified key CSF protein biomarkers of J.E. patients. We compared them to those from non-JE acute encephalitis syndrome and other neurological non-infectious patients to determine their discriminatory potential to detect JEV infection. Demographic and clinical information including fever, headache, vomiting, altered sensorium, behavioral abnormalities, neck stiffness, and GCS score were recorded for all patients. CSF protein biomarkers were analyzed using 2D gel electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total 22 CSF based protein biomarkers were identified and a out of them three protein spots were further processed for biomarkers identification on the basis of size and density. Functional enrichment analyses of Gene Ontology (G.O.) were performed using Cytoscape software to explore the biological functions and relevant pathways. G.O. enrichment analysis showed that the G.O. terms were mainly enriched in immune responses, inflammatory and apoptotic cell death pathways, autophagy regulation, cellular organization, cellular protein modification, lipid transportation, fatty acid metabolism and iron regulation specifically associated with JEV disease. Taken together, it showed that a combination of multiple CSF protein biomarkers constitutes a founding set for the discrimination of JEV infection individuals, which can be used for diagnosis and therapeutic targets; however, it demands further extensive independent cohorts study.