Impact of hepatitis C virus infection in B cells on pathogenesis

丙型肝炎病毒（HCV）感染导致肝脏疾病以及肝外疾病如B细胞非霍迪金淋巴瘤（B-NHL）的发展。为了揭示HCV相关B-NHL发展的分子信号通路，我们利用了在B细胞中特异性表达全长HCV基因组的转基因（Tg）小鼠，并发展为非霍奇金型B细胞淋巴瘤（BCL）。采用全基因组芯片技术分析了BCL-HCV-Tg小鼠、BCL-HCV-Tg小鼠和BCL-HCV-阴性小鼠的B细胞基因表达谱，并对BCLs中Fos、C3、LTbR、A20、NF-k B和miR-26 B进行了特异性分析。我们认为经典和替代NF-kB信号通路的激活以及miR-26 b的下调有助于HCV相关B-NHL的发展。

Hepatitis C virus (HCV) infection leads to the development of hepatic diseases, as well as extra hepatic disorders such as B-cell non-Hodikin's lymphoma (B-NHL). To reveal the molecular signaling pathways responsible for HCV-associated B-NHL development, we utilized 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-deceloping HCV-Tg mice, and from BCL-non-developing HCV-negative mice were analyzed by genome-wide microarray.Markedly modified genes such as Fos, C3, LTbR, A20, NF-kB and miR-26b in BCLs were further characterized using specific assays. We propose that activation of both canonical and alternative NF-kB signaling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.