Dataset Information

Altered brain pathways following Chikungunya virus infection

ABSTRACT: A kinetic analysis of host proteome modifications in the brain of CHIKV-infected mice sampled before and after the onset of clinical symptoms was performed. The combination of 2D-DIGE and iTRAQ proteomic approaches, followed by mass spectrometry protein identification, revealed 177 significantly differentially expressed proteins. This kinetic analysis was characterized by a dramatic down-regulation of proteins prior the appearance of the clinical symptoms followed by an increase expression of a large part of these proteins in the acute phase of symptoms. Bioinformatic analysis of the protein dataset allowed to identify major biological processes altered during the time course of CHIKV infection such as integrin signaling and cytoskeleton dynamics, endosome machinery and receptor recycling related to virus transport and synapse function, regulation of gene expression, and ubiquitin-proteasome pathway. This work gives new information on putative mechanisms that could be associated with severe neurological CHIKV infection-mediated disease. It also describes possible markers or targets that can be used to develop diagnostic and/or antiviral tools.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Chikungunya

SUBMITTER: Lionel Almeras

LAB HEAD: Pr. Christophe ROGIER

PROVIDER: PXD000736 | Pride | 2015-07-07

REPOSITORIES: Pride

ACCESS DATA

Publications

Kinetic analysis of mouse brain proteome alterations following Chikungunya virus infection before and after appearance of clinical symptoms.

Fraisier Christophe C Koraka Penelope P Belghazi Maya M Bakli Mahfoud M Granjeaud Samuel S Pophillat Matthieu M Lim Stephanie M SM Osterhaus Albert A Martina Byron B Camoin Luc L Almeras Lionel L

PloS one 20140311 3

Recent outbreaks of Chikungunya virus (CHIKV) infection have been characterized by an increasing number of severe cases with atypical manifestations including neurological complications. In parallel, the risk map of CHIKV outbreaks has expanded because of improved vector competence. These features make CHIKV infection a major public health concern that requires a better understanding of the underlying physiopathological processes for the development of antiviral strategies to protect individuals ...[more]

PMID: 24618821

Similar Datasets

Project description:West Nile virus (WNV) and Chikungunya virus (CHIKV) are arboviruses that are constantly (re)-emerging and expanding their territory. Both viruses often cause a mild form of disease, but severe forms of the disease can consist of neurological symptoms, most often observed in young children and the elderly, which are poorly understood. To elucidate the mechanisms responsible for end-stage WNV and CHIKV neuroinvasive disease and pathogenesis, we used transcriptomics to compare the effector pathways in the brain during the early and late stage of disease in young mice. Mice were infected with WNV strain NY99 (accession AF196835.2, obtained from the Health Protection Agency, Porton Down, UK; P5 on Vero E6 cells) or CHIKV strain S27, accession AF369024). Nine-day old female C57/BL6 mice were inoculated intraperitoneally with either 10^5 TCID50/100 µL of WNV-NY99 (n=6) or 10^6.5 TCID50/100 µL of CHIKV-S27 (n=6), or mock-infected. Mice were sacrificed 2, 3 or 5 days post-innoculation depending on the virus. For transcriptomic analysis, cerebellum was separated from the brain and the right hemisphere was gently washed once in ice-cold PBS and stored in RNAlater® (Thermo Fisher Scientific, Bleiswijk, The Netherlands) until further processing. Total RNA was isolated from the brain samples using Trizol Reagentand the RNEasy Mini kit. RNA (200 ng) was labeled using the MessageAmp Premier RNA Amplification kit (Applied Biosystems) and hybridized to Affymetrix GeneChip® Mouse 4302 Arrays. Image analysis was performed using GeneChip Operating Software. Microarray Suite version 5.0 software (Affymetrix) was used to generate .dat and .cel files for each experiment. Using this approach, we find evidence for a strong inflammatory response was found in mice infected with WNV and CHIKV. The transcriptomics profile measured in mice with WNV and CHIKV neuroinvasive disease in our study showed strong overlap with the mRNA profile described in the literature for other viral neuroinvasive diseases.

Dataset Information

Altered brain pathways following Chikungunya virus infection

Publications

Kinetic analysis of mouse brain proteome alterations following Chikungunya virus infection before and after appearance of clinical symptoms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure