B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling.
B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling.
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DOI：
10.1371/journal.pone.0091373
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tsukiyama-Kohara K
中科院分区：
文献类型：
--
作者：
Kasama Y;Mizukami T;Kusunoki H;Peveling-Oberhag J;Nishito Y;Ozawa M;Kohara M;Mizuochi T;Tsukiyama-Kohara K
丙型肝炎病毒（HCV）感染导致肝脏疾病以及肝外病症如B细胞非霍奇金淋巴瘤（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）。通过全基因组微阵列分析BCL-发展HCV-Tg小鼠、BCL-非发展HCV-Tg小鼠和BCL-非发展HCV阴性小鼠的B细胞中的基因表达谱。在来自HCV-Tg小鼠的BCL中，各种基因的表达被修饰，并且对于某些基因，表达受到动物性别的影响。使用特定测定进一步表征BCL中显著修饰的基因，如Fos、C3、LTβR、A20、NF-κB和miR-26 B。我们认为经典和替代NF-κB信号通路的激活和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 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, LTβR, A20, NF-κB and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-κB signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.
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