HBV cccDNA通过破坏宿主染色质三维结构抑制抗病毒基因MAU2的表达  

HBV cccDNA Inhibits the Expression of Antiviral Gene MAU2 by Disrupting the Three-dimensional Structure of Host Chromatin

作　　者：沈从乐 李韦杰 任博[1] 王雅杰 SHEN Congle;LI Weijie;REN Bo;WANG Yajie(Laboratory Department of Beijing Ditan Hospital Affiliated to Capital Medical University,Beijing 100015,China)

机构地区：[1]首都医科大学附属北京地坛医院,北京100015

出　　处：《病毒学报》2023年第6期1607-1614,共8页Chinese Journal of Virology

基　　金：国家自然科学基金(项目号:82102378),题目:HBV通过干扰宿主19p13.11增强子与MAU2基因的染色质三维构象促进自身复制的机制研究。

摘　　要：HBV cccDNA的持续存在是慢乙肝难以治愈的重要原因。研究发现HBV cccDNA会在空间距离上靠近宿主染色体的转录活跃区域,提示HBV能够借助宿主基因组的转录开放环境促进自身复制。但具体作用方式尚未阐明。本研究将通过染色质构象捕获技术检测19p13.11增强子与潜在靶基因MAU2的染色质空间构象变化,探究HBV对宿主基因MAU2染色质空间构象的破坏作用,明确HBV对MAU2基因表达的抑制,并同时验证MAU2的抗病毒功能。结果显示,MAU2是19p13.11增强子的下游靶基因,HBV cccDNA能够通过影响MAU2基因与19p13.11增强子之间原有的染色质三维构象抑制MAU2的表达,而MAU2能够反向抑制HBV的复制转录。本研究将为了解HBV的转录调控机制以及寻找更多抗病毒因子提供新的思路。Persistence of HBV cccDNA is an important reason for why chronic hepatitis B is difficult to cure.Research has showed that HBV cccDNA approaches the transcriptional active region of the host chromosome in spatial distance,indicating that HBV can promote its own replication through the transcriptional open environment of the host genome.But the specific mode of action has not been clarified.This study utilizes chromatin conformation capture technology to detect changes in the chromatin spatial conformation of 19p13.11enhancer and potential target gene MAU2,explore the destructive effect of HBV on the chromatin spatial conformation of the host gene MAU2,clarify the inhibition of MAU2 gene expression by HBV,and verify the antiviral function of MAU2.The results showed that MAU2 is a downstream target gene of 19p13.11 enhancer.HBV cccDNA can inhibit the expression of MAU2 by affecting the original chromatin three-dimensional conformation between MAU2 gene and 19p13.11 enhancer,while MAU2 can reverse inhibit HBV replication and transcription.This study will provide new ideas for understanding the transcriptional regulation mechanism of HBV and searching for more antiviral factors.

关 键 词：HBV MAU2 染色质三维结构 

分 类 号：R373.2[医药卫生—病原生物学]