Altered brain pathways following Chikungunya virus infection

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.