社论|第 77 卷，第 4 期，P903-905，2022 年 10 月 1 日 抑制细胞间

StephenW

社论|第 77 卷，第 4 期，P903-905，2022 年 10 月 1 日
抑制细胞间传播以达到 HDV 治愈：IFN-α 的重要性

    PDF [1 MB]
    数字
    节省
    分享
        再版
        要求
    最佳

抑制细胞间传播以达到 HDV 治愈：IFN-α 的重要性

    朱莉·卢西弗拉
    埃洛伊·R·维里尔 $
    托马斯·F·鲍默特 $
    显示脚注

发布时间：2022年8月8日DOI：https://doi.org/10.1016/j.jhep.2022.07.015
PlumX 指标

   
见文章，第 957–966 页
虽然 HBV 通过建立稳定的游离 DNA 持续存在于细胞中，[1]
HDV 被认为是通过病毒传播在受感染的生物体中维持的。这一假设源于我们对 HDV 生命周期的了解，包括产生编辑的基因组和抑制其复制的 HDV 形态发生所必需的病毒蛋白 (L-HDAg)。 [2]
现在，Zhang 及其同事报告了 HDV RNA 的短半衰期 [3]
这将不允许在非分裂细胞中维持 HDV。尽管怀疑在小鼠中存在长期 HDV 持续存在的细胞，[4]
,[5]
HDV 传播被认为完全是由于 HBV 包膜被劫持以分泌和重新感染幼稚细胞。 [2]
几种旨在治愈 HDV 感染的治疗方案已进入临床（综述于 [6]
和图1）。 Bulevirtide（以前称为 Myrcludex-B）是一种肽，它通过与病毒竞争与 NTCP 受体的结合来阻止 HDV 进入细胞（图 1）。 Lonafarnib 是一种法尼基转移酶抑制剂，最初设计用于减少 HDV 颗粒的分泌，因为 L-HDAg 需要法尼基化才能与 HBV 包膜蛋白相互作用（图 1）。最近的一项研究报告说，剩余的释放颗粒（逃避法尼基转移酶抑制剂的规范功能）大多是非传染性的，特别是因为它们包含 HDV 基因组的编辑版本[7]
（图。1）。据报道，核酸聚合物 (NAP) 可能通过阻断 HBsAg 释放来作用于病毒出口[8]
（图。1）。然而，仅通过其与 HBV 包膜的分泌发生 HDV 的传播并不能解释如何在接受肝移植和接受抗 HBsAg 治疗的患者中维持 HDV，[9]
或在 HDV 单感染小鼠中。 [4]
此外，bulevirtide、lonafarnib 或 NAP 的临床试验结果以及 bulevirtide 的首次现实生活研究（2020 年获得 EMA 的有条件授权）表明，这两种药物的抗病毒作用在用于单一疗法和当与 IFN-α 联合使用时，对 HDV 患者变得非常有效。 [10]

StephenW

Editorial| Volume 77, ISSUE 4, P903-905, October 01, 2022
Inhibiting cell-to-cell transmission to reach HDV cure: The importance of IFN-α

    PDF [1 MB]
    Figures
    Save
    Share
        Reprints
        Request
    Top

Inhibiting cell-to-cell transmission to reach HDV cure: The importance of IFN-α

    Julie Lucifora
    Eloi R. Verrier $
    Thomas F. Baumert $
    Show footnotes

Published:August 08, 2022DOI:https://doi.org/10.1016/j.jhep.2022.07.015
PlumX Metrics

   
See Article, pages 957–966
While HBV persists in cells through the establishment of stable episomal DNA,[1]
HDV is thought to be maintained in infected organisms by viral spreading. This hypothesis arose from our knowledge of the HDV life cycle that includes the production of an edited genome and a viral protein (L-HDAg) necessary for HDV morphogenesis that inhibits its replication.[2]
This is now enforced by Zhang and colleagues reporting a short half-life of HDV RNAs[3]
that would not allow HDV maintenance in non-dividing cells. Although the existence of long-term HDV persistence in cells was suspected in mice,[4]
,[5]
HDV spreading was thought to occur exclusively thanks to the hijacking of HBV envelope for its secretion and re-infection of naïve cells.[2]
Several therapeutic options aiming to cure HDV infection have entered the clinic (reviewed in[6]
and Fig. 1). Bulevirtide (previously called Myrcludex-B) is a peptide that blocks HDV entry into cells by competing with the virus for its binding to the NTCP receptor (Fig. 1). Lonafarnib, a farnesyl transferase inhibitor was initially designed to decrease the secretion of HDV particles since L-HDAg needs to be farnesylated to interact with the HBV envelope proteins (Fig. 1). A recent study reported that the remaining released particles (escaping the canonical function of farnesyl transferase inhibitor) are mostly non-infectious, notably because they contain an edited version of the HDV genome[7]
(Fig. 1). Nucleic acid polymers (NAPs) were also reported to potentially act on viral egress by blocking HBsAg release[8]
(Fig. 1). However, spreading of HDV occurring exclusively through its secretion with HBV envelope would not explain how HDV can be maintained in patients undergoing liver transplantation and receiving anti-HBsAg therapies,[9]
or in HDV-monoinfected mice.[4]
Moreover, results from clinical trials with bulevirtide, lonafarnib or NAPs and the first real-life studies for bulevirtide (that received conditional authorization by the EMA in 2020) suggested that the antiviral effects of either of the drugs are rather limited when used in monotherapy and become very potent for patients with HDV when combined with IFN-α.[10]

StephenW

http://www.journal-of-hepatology.eu/article/S0168827822029786/pdf