B-Cell-Intrinsic Hepatitis C Virus Expression Leads To B-Cell-Lymphomagenesis And Induction Of Nf-Kappa B Signalling

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, LT beta R, A20, NF-kappa B and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-kappa B signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.