Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications.
Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications.
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DOI：
10.1016/j.jhep.2016.02.011
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发表时间：
2016-04
影响因子：
25.7
通讯作者：
Urban S
中科院分区：
文献类型：
--
作者：
Li W;Urban S
在发现人类乙型肝炎病毒（HBV）后的近三十年里，病毒感染的早期事件（附着于肝细胞，特异性结合肝细胞上的受体）仍然是一个谜。随着HBV组织培养系统的逐步完善，已经能够鉴定出病毒传染性的决定因素，并促进了人类牛磺胆酸钠共转运多肽（hNTCP）作为HBV及其卫星病毒——人类丁型肝炎病毒（HDV）的肝脏特异性受体的发现。这些发现目前正在引领基础和临床研究活动向新的方向发展。(1)稳定的表达hntcp的细胞系已成为研究HBV从其天然模板cccDNA完整复制周期的有价值的平台。(2) NTCP补充细胞培养系统对高通量筛选方法的适用性将有助于鉴定参与HBV复制的新型宿主因子（包括那些决定HBV感染的特殊宿主特异性的因子），并将使鉴定和开发用于改进治疗的新型候选药物成为可能。(3)由于NTCP是HBV和HDV的主要宿主特异性限制因子，因此表达hntcp的动物为未来的体内易感模型提供了基础。(4)利用进入抑制剂Myrcludex B获得的概念表明，NTCP是临床干扰病毒进入的合适靶点。这将进一步促进旨在治疗性联合疗法的临床方法。
For almost three decades following the discovery of the human Hepatitis B Virus (HBV) the early events of virus infection (attachment to hepatocytes, specific binding to a receptor on hepatocytes) remained enigmatic. The gradual improvement of tissue culture systems for HBV has enabled the identification of viral determinants for viral infectivity and facilitated the discovery of the human sodium taurocholate co-transporting polypeptide (hNTCP) as a liver specific receptor of HBV and its satellite, the human Hepatitis Delta Virus (HDV). These findings are currently leading basic and clinical research activities in new directions. (1) Stable hNTCP-expressing cell lines have become a valuable platform to study the full HBV replication cycle from its native template, the cccDNA. (2) The suitability of NTCP complemented cell culture systems for high throughput screening approaches will facilitate identification of novel host factors involved in HBV replication (including those that determine the peculiar host specificity of HBV infection) and will enable identification and development of novel drug candidates for improved therapeutics. (3) Since NTCP is a major host-specific restriction factor for HBV and HDV, hNTCP-expressing animals provide the basis for future susceptible in vivo models. (4) The concept obtained with the entry inhibitor Myrcludex B demonstrates that NTCP is a suitable target for clinical interference with viral entry. This will foster further clinical approaches aiming at curative combination therapies.
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