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Transcriptome Profiling of Japanese Encephalitis Virus (JEV) Infected Human Neuroepithelioma Cells (SK-N-MC)

ABSTRACT: Japanese Encephalitis (JE) is an important causal of viral encephalitis in Eastern and Southeast Asia. Neuronal injury and varying degrees of neuroinflammation are often pathological hallmarks of JE, which result in high morbility and mortality rates. However, a clear understanding on neuron cells' responses to JEV infection remains elusive. This study, therefore, utilized the Affymetrix Human PrimeView array for a robust profiling of JEV infected SK-N-MC cells during the active phase of infection in order to investigate the molecular details of the host cell responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE115167 | GEO | 2018/11/20

REPOSITORIES: GEO

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Project description:- Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, and leading cause of neurological infection in Asia and the Pacific, with recent emergence in multiple territories in Australia in 2022. Patients may experience devastating socioeconomic consequences; JEV infection (JE) predominantly affects children in poor rural areas, has a 20-30% case fatality rate, and 30-50% of survivors suffer long-term disability. JEV RNA is rarely detected in patient samples, and the standard diagnostic test is an anti-JEV IgM ELISA with sub-optimal specificity; there is no means of detection in more remote areas. We aimed to test the hypothesis that there is a diagnostic protein signature of JE in human cerebrospinal fluid (CSF), and contribute to understanding of the host response and predictors of outcome during infection. We retrospectively tested a cohort of 163 patients recruited as part of the Laos central nervous system infection study. Application of liquid chromatography and tandem mass spectrometry (LC-MS/MS), using extensive offline fractionation and tandem mass tag labelling, enabled a comparison of the CSF proteome in 68 JE patient vs 95 non-JE neurological infections. 5,070 proteins were identified, including 4,805 human proteins and 265 pathogen proteins. We incorporated univariate analysis of differential protein expression, network analysis and machine learning techniques to build a ten-protein diagnostic signature of JE with >99% diagnostic accuracy. Pathways related to JE infection included neuronal damage, anti-apoptosis, heat shock and unfolded protein responses, cell adhesion, macrophage and dendritic cell activation as well as a reduced acute inflammatory response, hepatotoxicity, activation of coagulation, extracellular matrix and actin regulation. We verified the results by performing DIA LC-MS/MS in 16 (10%) of the samples, demonstrating 87% accuracy using the same model. Ultimately, antibody-based validation will be required, in a larger group of patients, in different locations and in field settings, to refine the list to 2-3 proteins that could be harnessed in a rapid diagnostic test.

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Transcriptome Profiling of Japanese Encephalitis Virus (JEV) Infected Human Neuroepithelioma Cells (SK-N-MC)

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