Impact of hepatitis C virus infection in B cells on pathogenesis

B细胞丙型肝炎病毒感染对发病机制的影响

• 批准号: 23590547
• 负责人: KOHARA Kyoko
• 金额: $ 3.33万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590547/
• 关键词: C型肝炎ウイルス; Bリンパ腫; microarray; A20; NF-kB; miR-26b; Ｂリンパ腫; トランスジェニックマウス; microRNA

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.

丙型肝炎病毒感染会导致肝脏疾病的发展，也会导致肝外疾病，如B细胞性非霍迪金淋巴瘤(B-NHL)。为了揭示与丙型肝炎病毒相关的B-NHL发生的分子信号通路，我们利用了在B细胞中特异表达全长丙型肝炎病毒基因组的转基因(TG)小鼠，并患上了非霍奇金型B细胞淋巴瘤(BCL)。用全基因组芯片分析bcl型、bcl型和非bcl型丙型肝炎病毒阴性小鼠B细胞的基因表达谱，并进一步用特异的方法鉴定BCLs中的Fos、C3、LTbR、A20、NF-kB和miR-26b等基因。我们认为，规范的和替代的NF-kB信号通路的激活以及miR-26b的下调有助于丙型肝炎病毒相关性B-NHL的发展。

项目成果

Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

• DOI: 10.1371/journal.pone.0059611
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Nakagawa S;Hirata Y;Kameyama T;Tokunaga Y;Nishito Y;Hirabayashi K;Yano J;Ochiya T;Tateno C;Tanaka Y;Mizokami M;Tsukiyama-Kohara K;Inoue K;Yoshiba M;Takaoka A;Kohara M
• 通讯作者: Kohara M

型肝炎ウイルス誘導性酸化ストレスによる肝細胞腫瘍原性更新

肝炎病毒诱导的氧化应激导致肝细胞致瘤更新

• 发表时间: 2013
• 作者: Toda T;et al;小原恭子
• 通讯作者: 小原恭子

Chronic hepatitis C virus model in Tupaia belangeri

树鼩慢性丙型肝炎病毒模型

• 发表时间: 2013
• 作者: Tsukiyama-Kohara K;Amako Y;Kohara M
• 通讯作者: Kohara M

C型肝炎ウイルスのBリンパ腫発症要因の解明

阐明丙型肝炎病毒乙型淋巴瘤发展的原因

• 发表时间: 2013
• 作者: 笠間由里;小原道法;小原恭子,
• 通讯作者: 小原恭子,

Antibody against 3β-Hydroxysterol-Δ24-Reductase Suppresses Hepatitis C Virus Infection through Betaine/GABA Transporter-1

抗 3β-羟基甾醇-Δ24-还原酶抗体通过甜菜碱/GABA 转运蛋白 1 抑制丙型肝炎病毒感染

• 发表时间: 2012
• 作者: Satoh;M.;Kohara;M.;Tsukiyama-Kohara;K.
• 通讯作者: K.