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PLoS One. 2014 Mar 11;9(3):e91397. doi: 10.1371/journal.pone.0091397. eCollection 2014.

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

Author information

1
Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France.
2
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
3
Aix-Marseille Université, CNRS, CRN2M UMR 7286, Marseille, France.
4
CRCM, Marseille Protéomique, Inserm, U1068, Marseille, France; Aix-Marseille Université, UM 105, Marseille, France.
5
Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France; Unité de recherche en biologie et épidémiologie parasitaires (URBEP), Institut de Recherche Biomédicale des Armées (IRBA), Marseille, France.

Abstract

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 from severe disease. To decipher the mechanisms of CHIKV infection in the nervous system, a kinetic analysis on the 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 revealed a dramatic down-regulation of proteins before the appearance of the clinical symptoms followed by the increased expression of most of these proteins in the acute symptomatic phase. Bioinformatic analyses of the protein datasets enabled the identification of the major biological processes that were 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 the ubiquitin-proteasome pathway. These results reveal the putative mechanisms associated with severe CHIKV infection-mediated neurological disease and highlight the potential markers or targets that can be used to develop diagnostic and/or antiviral tools.

PMID:
24618821
PMCID:
PMC3949995
DOI:
10.1371/journal.pone.0091397
[Indexed for MEDLINE]
Free PMC Article
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