title: Hepatitis C virus-related lymphomagenesis in a mouse model.
abstract: B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1(_/_)/CN2 mice). Irf-1(_/_)/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes.
authors.affiliation: Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto 860-8556, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsukiyama-Kohara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kasama
authors.forename: Nagla Elwy
authors.initials: NE
authors.lastname: Salem
authors.forename: Keigo
authors.initials: K
authors.lastname: Machida
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
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