[推荐]整合的乙型肝炎病毒 DNA 在抗病毒治疗期间维持表面抗

StephenW

整合的乙型肝炎病毒 DNA 在抗病毒治疗期间维持表面抗原的产生
Tanner Grudda,1 Hyon S. Hwang,2 Maraake Taddese,2 Jeffrey Quinn,2 Mark S. Sulkowski,2 Richard K. Sterling,3 Ashwin Balagopal,2 和 Chloe L. Thio1,2

2022 年 7 月 7 日发布 - 更多信息
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乙型肝炎的功能性治愈需要沉默共价闭合环状和整合的乙型肝炎病毒 DNA
马克 G. 加尼、安娜 S. 乐
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    抽象的

    乙型肝炎功能性治愈（定义为乙型肝炎病毒（HBV）表面抗原（HBsAg）和血液中的HBV DNA持续丢失）的重点是消除或沉默HBV复制的核内模板，即共价闭合环状DNA（cccDNA）。然而，HBsAg 也来源于整合到宿主基因组 (iDNA) 中的 HBV DNA。目前的治疗方法对 iDNA 对循环 HBsAg 的贡献知之甚少。我们应用了多重液滴数字 PCR 测定来证明 iDNA 负责维持某些个体的 HBsAg 数量。我们使用来自 16 名接受核苷（酸）类似物 (NUC) 治疗的 HIV/HBV 合并感染者的成对大块肝组织，证明在活检之间 HBsAg 下降幅度较大的人从 cccDNA 获得 HBsAg，而 HBsAg 水平稳定的人主要从 iDNA 获得.我们将我们的分析应用于来自 3 人的配对组织中的单个肝细胞，并证明具有显着 HBsAg 下降的个体具有相应的具有转录活性 cccDNA 的感染细胞损失，而没有 HBsAg 下降的个体具有稳定或增加数量的从 iDNA 产生 HBsAg 的细胞.我们证明，虽然 NUC 治疗可能有效控制 cccDNA 复制和转录，但需要创新治疗来解决维持 HBsAg 产生的 iDNA 转录。

StephenW

Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment
Tanner Grudda,1 Hyon S. Hwang,2 Maraake Taddese,2 Jeffrey Quinn,2 Mark S. Sulkowski,2 Richard K. Sterling,3 Ashwin Balagopal,2 and Chloe L. Thio1,2

Published July 7, 2022 - More info
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Functional cure of hepatitis B requires silencing covalently closed circular and integrated hepatitis B virus DNA
Marc G. Ghany, Anna S. Lok
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    Abstract

    The focus of hepatitis B functional cure, defined as sustained loss of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA from blood, is on eliminating or silencing the intranuclear template for HBV replication, covalently closed circular DNA (cccDNA). However, HBsAg also derives from HBV DNA integrated into the host genome (iDNA). Little is known about the contribution of iDNA to circulating HBsAg with current therapeutics. We applied a multiplex droplet digital PCR assay to demonstrate that iDNA is responsible for maintaining HBsAg quantities in some individuals. Using paired bulk liver tissue from 16 HIV/HBV-coinfected persons on nucleos(t)ide analog (NUC) therapy, we demonstrate that people with larger HBsAg declines between biopsies derive HBsAg from cccDNA, whereas people with stable HBsAg levels derive predominantly from iDNA. We applied our assay to individual hepatocytes in paired tissues from 3 people and demonstrated that the individual with significant HBsAg decline had a commensurate loss of infected cells with transcriptionally active cccDNA, while individuals without HBsAg decline had stable or increasing numbers of cells producing HBsAg from iDNA. We demonstrate that while NUC therapy may be effective at controlling cccDNA replication and transcription, innovative treatments are required to address iDNA transcription that sustains HBsAg production.

StephenW

https://doi.org/10.1172/jci163175

lancas

还是DNA~而且现在进展也并不顺利~~~