title: B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling.
abstract: Hepatitis C virus (HCV) infection leads to the development of hepatic diseases, as well as extrahepatic disorders such as B-cell non-Hodgkin's lymphoma (B-NHL). To reveal the molecular signalling pathways responsible for HCV-associated B-NHL development, we utilised transgenic (Tg) mice that express the full-length HCV genome specifically in B cells and develop non-Hodgkin type B-cell lymphomas (BCLs). The gene expression profiles in B cells from BCL-developing HCV-Tg mice, from BCL-non-developing HCV-Tg mice, and from BCL-non-developing HCV-negative mice were analysed by genome-wide microarray. In BCLs from HCV-Tg mice, the expression of various genes was modified, and for some genes, expression was influenced by the gender of the animals. Markedly modified genes such as Fos, C3, LTβR, A20, NF-κB and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-κB signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.
authors.affiliation: Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, Kumamoto-shi, Kumamoto, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kasama
authors.affiliation: Department of Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashi-Murayama-shi, Tokyo, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: Department of Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashi-Murayama-shi, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kusunoki
authors.affiliation: Department of Internal Medicine, Goethe-University Hospital, Frankfurt, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Peveling-Oberhag
authors.affiliation: Center for Microarray Analysis, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Tokyo, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishito
authors.affiliation: Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan; Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Tokyo, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.affiliation: Department of Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashi-Murayama-shi, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mizuochi
authors.affiliation: Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan; Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsukiyama-Kohara
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002467:Cell Nucleus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000821:virology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport; D015398:Signal Transduction / Q000235:genetics; D012984:Software; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D016328:NF-kappa B; D009363:Neoplasm Proteins; D051996:Transcription Factor RelA