Effect of HCV in B cells and changes in B cell lymphoma (BCL). Mus musculus

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, LTbetaR, A20, NF-kappaB and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-kappaB signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL. Overall design: Mouse expressing the full-genome HCV in B cells, effect of HCV in B cells and changes in BCL were characterized. Mouse HCV+ vs HCV- B cell, or HCV+ B cell vs HCV+ BCL of male or female mice.