title: Hepatocyte pathway alterations in response to in vitro Crimean Congo hemorrhagic fever virus infection.
abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus responsible for hemorrhagic manifestations and multiple organ failure, with a high mortality rate. In infected humans, damage to endothelial cells and vascular leakage may be a direct result of virus infection or an immune response-mediated indirect effect. The main target cells are mononuclear phagocytes, endothelial cells and hepatocytes; the liver being a key target for the virus, which was described as susceptible to interferon host response and to induce apoptosis. To better understand the early liver cell alterations due to virus infection, the protein profile of in vitro CCHFV-infected HepG2 cells was analyzed using two quantitative proteomic approaches, 2D-DIGE and iTRAQ. A set of 243 differentially expressed proteins was identified. Bioinformatics analysis (Ingenuity Pathways Analysis) revealed multiple host cell pathways and functions altered after CCHFV infection, with notably 106 proteins related to cell death, including 79 associated with apoptosis. Different protein networks emerged with associated pathways involved in inflammation, oxidative stress and apoptosis, ubiquitination/sumoylation, regulation of the nucleo-cytoplasmic transport, and virus entry. Collectively, this study revealed host liver protein abundances that were modified at the early stages of CCHFV infection, offering an unparalleled opportunity of the description of the potential pathogenesis processes and of possible targets for antiviral research.
authors.affiliation: Institut de Recherche Biomédicale des Armées (Armed Forces Biomedical Research Institute, IRBA), antenne Marseille, Unité de Parasitologie, URMITE UM 63, GSBdD de Marseille Aubagne, 111 avenue de la Corse BP 40026, 13568 Marseille Cedex 02, France; Aix-Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), UM 63, CNRS 7278, IRD 198, Inserm 1095, WHO Collaborative Center for Rickettsioses and Other Arthropod-borne Bacterial Diseases, Faculté de Médecine, 27 boulevard Jean Moulin, 13385 Marseille cedex 5, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraisier
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, 21 Avenue Tony Garnier, 69007 Lyon, France.
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodrigues
authors.affiliation: Institut de Recherche Biomédicale des Armées (Armed Forces Biomedical Research Institute, IRBA), antenne Marseille, Unité de Parasitologie, URMITE UM 63, GSBdD de Marseille Aubagne, 111 avenue de la Corse BP 40026, 13568 Marseille Cedex 02, France; Aix-Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), UM 63, CNRS 7278, IRD 198, Inserm 1095, WHO Collaborative Center for Rickettsioses and Other Arthropod-borne Bacterial Diseases, Faculté de Médecine, 27 boulevard Jean Moulin, 13385 Marseille cedex 5, France.
authors.forename: Vinh
authors.initials: V
authors.lastname: Vu Hai
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M, UMR 7286, 13015 Marseille, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Belghazi
authors.affiliation: Institut de Recherche Biomédicale des Armées (Armed Forces Biomedical Research Institute, IRBA), antenne Marseille, Unité de Parasitologie, URMITE UM 63, GSBdD de Marseille Aubagne, 111 avenue de la Corse BP 40026, 13568 Marseille Cedex 02, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bourdon
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, 21 Avenue Tony Garnier, 69007 Lyon, France.
authors.forename: Glaucia
authors.initials: G
authors.lastname: Paranhos-Baccala
authors.affiliation: Inserm, U1068, CNRS, UMR7258, CRCM, Aix-Marseille Univ, UM 105, Marseille F-13009, France; Institut Paoli-Calmettes, Marseille Protéomique, Marseille F-13009, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Camoin
authors.affiliation: Institut de Recherche Biomédicale des Armées (Armed Forces Biomedical Research Institute, IRBA), antenne Marseille, Unité de Parasitologie, URMITE UM 63, GSBdD de Marseille Aubagne, 111 avenue de la Corse BP 40026, 13568 Marseille Cedex 02, France; Aix-Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), UM 63, CNRS 7278, IRD 198, Inserm 1095, WHO Collaborative Center for Rickettsioses and Other Arthropod-borne Bacterial Diseases, Faculté de Médecine, 27 boulevard Jean Moulin, 13385 Marseille cedex 5, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Almeras
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, 21 Avenue Tony Garnier, 69007 Lyon, France; SFR Biosciences Gerland-Lyond Sud (UM53444/U58), France; Unité de virologie, Institut de Recherche Biomédicale des Armées (IRBA) antenne de Lyon, tour CERVI, 21 avenue Tony Garnier, 69007 Lyon cedex, France. Electronic address: cpeyrefitte2000@yahoo.fr.
authors.forename: Christophe Nicolas
authors.initials: CN
authors.lastname: Peyrefitte
mesh_terms: D000818:Animals; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000235:genetics / Q000502:physiology*; D006479:Hemorrhagic Fever, Crimean / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040901:Proteomics
chemical_list: D011506:Proteins
keywords: 2D-DIGE; Bunyaviridae; CCHFV; CME; Crimean-Congo hemorrhagic fever virus; FC; FDR; GO; IEF; IFN-I; IPA; IPG; Ingenuity Pathway Analysis; MOI; MS; Pathogenesis; Pathways deregulated; clathrin-mediated endocytosis; false discovery rate; fold-change; gene ontology; iTRAQ; immobilized pH gradient; interferon type I; isoelectric focusing; mass spectrometry; multiplicity of infection; p.i.; post infection