Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University , Guangzhou, China.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA.
J Virol. 2023 Oct 31;97(10):e0076023. doi: 10.1128/jvi.00760-23. Epub 2023 Sep 27.
The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3' terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3' truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3' DR1, respectively, indicating the 3' DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3' unprotected terminus, which is independent of pgRNA length and the 3' terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics.
近年来，血清 HBV pgRNA 的生物发生和临床应用一直是研究热点。本研究利用多种条件性支持 HBV 基因组复制和分泌的实验系统，进一步研究了衣壳 RNA 3'末端的异质性，揭示了衣壳 pgRNA 的 3'截断分别由细胞核糖核酸酶（s）和病毒 RNaseH 在 3' DR1 前后的位置催化，表明 3' DR1 是 pgRNA 逆转录的包裹部分和 3'未保护末端之间的边界，该边界独立于 pgRNA 长度和 3'末端序列。因此，我们的研究为 pgRNA 包裹和逆转录的机制以及血清 HBV RNA 诊断的优化提供了新的见解。
