Comparison of a human neuronal model proteome upon Japanese encephalitis or West Nile Virus infection and potential role of mosquito saliva in neuropathogenesis.

Nathalie Pardigon,Sandrine Gatellier,Justine Basset,Mariette Matondo,Valérie Choumet,Véronique Hourdel,Benoit Besson,Hélène Chabrolles,Thibault Chaze

doi:10.1371/journal.pone.0232585

Nathalie Pardigon, Sandrine Gatellier + Show 7 more

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https://doi.org/10.1371/journal.pone.0232585

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Abstract

Neurotropic flavivirus Japanese encephalitis virus (JEV) and West Nile virus (WNV) are amongst the leading causes of encephalitis. Using label-free quantitative proteomics, we identified proteins differentially expressed upon JEV (gp-3, RP9) or WNV (IS98) infection of human neuroblastoma cells. Data are available via ProteomeXchange with identifier PXD016805. Both viruses were associated with the up-regulation of immune response (IFIT1/3/5, ISG15, OAS, STAT1, IRF9) and the down-regulation of SSBP2 and PAM, involved in gene expression and in neuropeptide amidation respectively. Proteins associated to membranes, involved in extracellular matrix organization and collagen metabolism represented major clusters down-regulated by JEV and WNV. Moreover, transcription regulation and mRNA processing clusters were also heavily regulated by both viruses. The proteome of neuroblastoma cells infected by JEV or WNV was significantly modulated in the presence of mosquito saliva, but distinct patterns were associated to each virus. Mosquito saliva favored modulation of proteins associated with gene regulation in JEV infected neuroblastoma cells while modulation of proteins associated with protein maturation, signal transduction and ion transporters was found in WNV infected neuroblastoma cells.

Highlights

Arboviral diseases continue to represent a major burden for society, with both health and economic consequences
The genomic polyprotein of Japanese encephalitis virus (JEV) and West Nile virus (WNV) were highly detected in the infected cells, confirming an efficient infection of the cells by both viruses (S2 Fig)
To the best of our knowledge, we provide here the first proteomic comparison of JEV or WNV infected human neuroblastoma cells using a label-free quantification of whole-cell extract approach

Summary

Introduction

Arboviral diseases continue to represent a major burden for society, with both health and economic consequences. Japanese encephalitis virus (JEV) and West Nile virus (WNV), two closely-related Flavivirus [1], are the most important cause of encephalitis amongst arboviruses, leading to large outbreaks in Asia for the former, and is the principal cause of epidemic encephalitis in the United States, for the latter [2]. Other mosquito-borne flaviviruses can display neurotropic features such as dengue virus in rare cases, Saint-Louis encephalitis virus. Proteomic analysis of neuroblastoma infection by WNV and JEV

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