Table of Contents
ISRN Hematology
Volume 2011, Article ID 167501, 8 pages
Review Article

Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

1Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto 860-8556, Japan
2Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
3Department of Medical Virology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto 860-8556, Japan
4Clinical Pathology Department, Faculty of Medicine, Suez Canal University, Round Road Kilo 4.5, Ismailia, Egypt
5Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA

Received 5 May 2011; Accepted 2 June 2011

Academic Editors: D. Efremov and L. Visser

Copyright © 2011 Kyoko Tsukiyama-Kohara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.