B细胞淋巴瘤6（BCL6）是一种可以抑制HBV基因表达并调节免疫

StephenW

Front Microbiol. 2019 Jan 10;9:3253. doi: 10.3389/fmicb.2018.03253. eCollection 2018.
B-Cell Lymphoma 6 (BCL6) Is a Host Restriction Factor That Can Suppress HBV Gene Expression and Modulate Immune Responses.
Lin CT1,2, Hsieh YT1, Yang YJ1, Chen SH1, Wu CH1, Hwang LH1.
Author information

1
    Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
2
    Biomedical Industry Ph.D. Program, National Yang-Ming University, Taipei, Taiwan.

Abstract

Hepatitis B virus (HBV) infection causes acute and chronic liver inflammation. Recent studies have demonstrated that some viral antigens can suppress host innate and adaptive immunity, and thus lead to HBV liver persistency. However, the cellular factors that can help host cells to clear HBV during acute infection remain largely unknown. Here, we used HBV-cleared and HBV-persistent mouse models to seek for cellular factors that might participate in HBV clearance. HBV replicon DNA was delivered into the mouse liver by hydrodynamic injection. RNA-Seq analysis was conducted to identify immune-related genes that were differentially expressed in HBV-persistent and HBV-cleared mouse models. A cellular factor, B cell lymphoma 6 (BCL6), was found to be significantly upregulated in the liver of HBV-cleared mice upon HBV clearance. Co-expression of BCL6 and a persistent HBV clone rendered the clone largely cleared, implicating an important role of BCL6 in controlling HBV clearance. Mechanistic studies demonstrated that BCL6 functioned as a repressor, binding to and suppressing the activities of the four HBV promoters. Correspondingly, BCL6 expression significantly reduced the levels of HBV viral RNA, DNA, and proteins. BCL6 expression could be stimulated by inflammatory cytokines such as TNF-α; the BCL6 in turn synergized TNF-α signaling to produce large amounts of CXCL9 and CXCL10, leading to increased infiltrating immune cells and elevated cytokine levels in the liver. Thus, positive feedback loops on BCL6 expression and immune responses could be produced. Together, our results demonstrate that BCL6 is a novel host restriction factor that exerts both anti-HBV and immunomodulatory activities. Induction of BCL6 in the liver may ultimately assist host immune responses to clear HBV.
KEYWORDS:

B-cell lymphoma 6 (BCL6); HBV clearance; Hepatitis B virus (HBV); restriction factor; transcriptional repressor

PMID:
    30687256
PMCID:
    PMC6335256
DOI:
    10.3389/fmicb.2018.03253

StephenW

前微生物。 2019年1月10日; 9：3253。 doi：10.3389 / fmicb.2018.03253。 eCollection 2018。
B细胞淋巴瘤6（BCL6）是一种可以抑制HBV基因表达并调节免疫应答的宿主限制因子。
Lin CT1,2，Hsieh YT1，Yang YJ1，Chen SH1，Wu CH1，Hwang LH1。
作者信息

1
    台湾台北国立阳明大学微生物学与免疫学研究所。
2
    生物医学工业博士国立阳明大学，台湾台北。

抽象

乙型肝炎病毒（HBV）感染引起急性和慢性肝脏炎症。最近的研究表明，一些病毒抗原可以抑制宿主先天性和适应性免疫，从而导致HBV肝脏持续存在。然而，在急性感染期间可以帮助宿主细胞清除HBV的细胞因子仍然很大程度上未知。在这里，我们使用HBV清除和HBV持续性小鼠模型来寻找可能参与HBV清除的细胞因子。通过流体动力学注射将HBV复制子DNA递送到小鼠肝脏中。进行RNA-Seq分析以鉴定在HBV持久性和HBV清除的小鼠模型中差异表达的免疫相关基因。在HBV清除后，发现细胞因子B细胞淋巴瘤6（BCL6）在HBV清除的小鼠的肝脏中显着上调。 BCL6和持久性HBV克隆的共表达使得克隆在很大程度上被清除，暗示BCL6在控制HBV清除中的重要作用。机理研究表明，BCL6作为阻遏物起作用，结合并抑制四种HBV启动子的活性。相应地，BCL6表达显着降低了HBV病毒RNA，DNA和蛋白质的水平。 BCL6表达可被炎性细胞因子如TNF-α刺激; BCL6反过来协同TNF-α信号传导产生大量的CXCL9和CXCL10，导致肝脏中浸润的免疫细胞增加和细胞因子水平升高。因此，可以产生关于BCL6表达和免疫应答的正反馈回路。总之，我们的结果表明BCL6是一种新的宿主限制因子，可以发挥抗HBV和免疫调节活性。在肝脏中诱导BCL6可最终帮助宿主免疫应答以清除HBV。
关键词：

B细胞淋巴瘤6（BCL6）; HBV清除;乙型肝炎病毒（HBV）;限制因素;转录抑制因子

结论：
    30687256
PMCID：
    PMC6335256
DOI：
    10.3389 / fmicb.2018.03253

StephenW

https://www.frontiersin.org/arti ... icb.2018.03253/full