Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

Abstract EN

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.