[Post-transcriptional regulation mechanism and antiviral strategy of hepatitis B virus RNA]

Zhonghua Gan Zang Bing Za Zhi. 2024 May 20;32(5):474-480. doi: 10.3760/cma.j.cn501113-20240410-00191.
[Article in Chinese]

Abstract

Chronic hepatitis B virus (HBV) infection is one of the major public health issues of ongoing global concern. Due to inadequate understanding of the HBV life cycle, there is a lack of effective drugs to cure chronic hepatitis B. During HBV replication, covalently closed circular DNA (cccDNA) serves as the template for viral replication and can be transcribed to produce five viral RNAs of 3.5, 2.4, 2.1 kb and 0.7 kb in length, which are translated to produce HBeAg, core protein, polymerase (P) protein, HBsAg and HBx proteins, respectively. Among them, the 3.5 kb pregenomic RNA (pgRNA) is also the template for viral reverse transcription. Polymerase protein recognizes and binds to the capsid assembly signal on the pgRNA to initiate capsid assembly and reverse transcription. Recent studies have revealed that the processes of splicing, nuclear export, stability, translation, and pgRNA encapsidation of HBV RNAs are regulated by a post-transcriptional regulatory network within the host cell and depend on unique post-transcriptional regulatory elements in the HBV RNA structure. The aim of this review is to overview the post-transcriptional regulatory mechanisms of HBV RNA and their applications in the study of HBV antiviral therapeutics, with the aim of providing new ideas for the development of new drugs targeting HBV RNA.

慢性乙型肝炎病毒(HBV)感染是全球持续关注的重大公共健康问题之一。由于对HBV生命周期的认识还不够充分,目前尚缺乏有效治愈慢性乙型肝炎的药物。在HBV复制过程中,共价闭合环状DNA作为病毒复制的模板,可转录产生长度为3.5、2.4、2.1 kb以及0.7 kb的5种病毒RNA,分别翻译产生HBeAg、core蛋白、聚合酶(P)蛋白、HBsAg和HBx蛋白。其中,3.5 kb的前基因组RNA(pgRNA)也是病毒逆转录的模板,P蛋白可识别并结合pgRNA上的衣壳组装信号,启动衣壳组装和逆转录。近年来研究发现,HBV RNA的剪接、核输出、稳定性、翻译以及pgRNA衣壳化等过程均受到宿主细胞内的转录后调控网络调控,并依赖HBV RNA结构中独特的转录后调节元件。现对HBV RNA的转录后调控机制及其在HBV抗病毒治疗药物研究中的应用进行综述,以期为靶向HBV RNA的新药研发提供新思路。.

Keywords: Antivirulence; Chronic hepatitis B; Hepatitis B virus; Post-transcriptional regulation; Thera peutic.

Publication types

  • Review
  • English Abstract

MeSH terms

  • Antiviral Agents / pharmacology
  • Gene Expression Regulation, Viral
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / physiology
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / virology
  • Humans
  • RNA Processing, Post-Transcriptional
  • RNA, Viral* / metabolism
  • Virus Replication*

Substances

  • RNA, Viral
  • Antiviral Agents