title: Kinetic analysis of mouse brain proteome alterations following Chikungunya virus infection before and after appearance of clinical symptoms.
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.
authors.affiliation: Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraisier
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Penelope
authors.initials: P
authors.lastname: Koraka
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M UMR 7286, Marseille, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Belghazi
authors.affiliation: Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France.
authors.forename: Mahfoud
authors.initials: M
authors.lastname: Bakli
authors.affiliation: CRCM, Marseille Protéomique, Inserm, U1068, Marseille, France; Aix-Marseille Université, UM 105, Marseille, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Granjeaud
authors.affiliation: CRCM, Marseille Protéomique, Inserm, U1068, Marseille, France; Aix-Marseille Université, UM 105, Marseille, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Pophillat
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Osterhaus
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Byron
authors.initials: B
authors.lastname: Martina
authors.affiliation: CRCM, Marseille Protéomique, Inserm, U1068, Marseille, France; Aix-Marseille Université, UM 105, Marseille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Camoin
authors.affiliation: 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.
authors.forename: Lionel
authors.initials: L
authors.lastname: Almeras
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D065632:Chikungunya Fever / Q000175:diagnosis / Q000378:metabolism*; D002646:Chikungunya virus / Q000378:metabolism; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D053263:Gene Regulatory Networks; D007700:Kinetics; D051379:Mice; D020543:Proteome; D040901:Proteomics; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D000956:Antigens, Viral; D020543:Proteome