Virological Basis for the Cure of Chronic Hepatitis B.
Virological Basis for the Cure of Chronic Hepatitis B.
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DOI：
10.1021/acsinfecdis.8b00081
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发表时间：
2019-05-10
影响因子：
5.3
通讯作者：
Guo JT
中科院分区：
文献类型：
--
作者：
Hu J;Cheng J;Tang L;Hu Z;Luo Y;Li Y;Zhou T;Chang J;Guo JT
B型肝炎病毒（HBV）已感染世界三分之一的人口，其中2.4亿人为慢性携带者，至今仍无法治愈。与其他病毒类似，持续性HBV感染依赖于病毒利用宿主细胞功能来支持其复制，并有效地逃避宿主的先天性和适应性抗病毒免疫。因此，了解HBV复制和伴随的宿主细胞相互作用有助于开发治疗方法，以破坏对其持续性至关重要的病毒-宿主相互作用并治愈慢性乙型肝炎B。尽管目前可用的HBV感染的细胞培养系统难以对HBV复制所必需和/或调节HBV复制的关键宿主细胞因子进行全基因组高通量筛选，但过去几十年来经典的一次一个基因（或途径）的研究已经揭示了HBV-宿主相互作用的许多方面。HBV-肝细胞相互作用的概况表明，除了通过直接靶向病毒蛋白质更紧密地抑制病毒复制之外，破坏关键的病毒-宿主细胞相互作用以消除或消除共价闭合环状（ccc）DNA，其是最稳定的HBV复制中间体，作为感染肝细胞核中的附加体微型染色体存在，是实现慢性B型肝炎功能性治愈所必需的。此外，整合的HBV DNA及其转录物的治疗靶向也可能需要诱导HBsAg血清清除和预防肝癌发生。
Hepatitis B virus (HBV) has infected one-third of world population and 240 million people are chronic carriers, to whom a curative therapy is still not available. Similar to other viruses, persistent HBV infection relies on the virus to exploit host cell functions to support its replication and efficiently evade host innate and adaptive antiviral immunity. Understanding HBV replication and concomitant host cell interactions is thus instrumental for development of therapeutics to disrupt the virus-host interactions critical for its persistence and cure chronic hepatitis B. Although the currently available cell culture systems of HBV infection are refractory to genome-wide high throughput screening of key host cellular factors essential for and/or regulating HBV replication, classic one-gene (or pathway)-at-a-time studies in last several decades have already revealed many aspects of HBV-host interactions. An overview of the landscape of HBV-hepatocyte interaction indicates that in addition to more tightly suppressing viral replication by directly targeting viral proteins, disruption of key viral-host cell interactions to eliminate or inactivate the covalently closed circular (ccc) DNA, the most stable HBV replication intermediate that exists as an episomal minichromosome in the nucleus of infected hepatocyte, is essential to achieve a functional cure of chronic hepatitis B. Moreover, therapeutic targeting of integrated HBV DNA and their transcripts may also be required to induce HBsAg seroclearance and prevent liver carcinogenesis.
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DOI：
10.3390/v9010021
发表时间：
2017-01-21
期刊：
Viruses
影响因子：
--
作者：
Gallucci L;Kann M
通讯作者：
Kann M
影响因子：
5.4
作者：
Altinel K;Hashimoto K;Wei Y;Neuveut C;Gupta I;Suzuki AM;Dos Santos A;Moreau P;Xia T;Kojima S;Kato S;Takikawa Y;Hidaka I;Shimizu M;Matsuura T;Tsubota A;Ikeda H;Nagoshi S;Suzuki H;Michel ML;Samuel D;Buendia MA;Faivre J;Carninci P
通讯作者：
Carninci P
影响因子：
5.4
作者：
Benhenda, Shirine;Ducroux, Aurelie;Neuveut, Christine
通讯作者：
Neuveut, Christine
影响因子：
5.4
作者：
Daub, H;Blencke, S;Cotten, M
通讯作者：
Cotten, M
影响因子：
7.6
作者：
Guo JT;Guo H
通讯作者：
Guo H