School of Biological and Chemical Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA; email:
Annu Rev Virol. 2020 Sep 29;7(1):189-202. doi: 10.1146/annurev-virology-012720-094902.
Host cell factors are integral to viral replication. Human immunodeficiency virus 1 (HIV-1), the retroviral agent of acquired immune deficiency syndrome, requires several host factors for reverse transcription of the viral genomic RNA (gRNA) into DNA shortly after viral entry. One of these host factors is the RNA lariat debranching enzyme (Dbr1), which cleaves the 2'-5' bond of branched and lariat RNAs. A recent study has revealed that Dbr1 cleaves HIV-1 gRNA lariats that form early after viral entry. Without Dbr1 activity, HIV-1 reverse transcription stalls, consistent with blockage of viral reverse transcriptase at gRNA branch points. These findings echo an earlier study with the long-terminal-repeat retrotransposon of , Ty1, which is a retrovirus model. Currently, branching and debranching of viral gRNA are not widely recognized as features of HIV-1 replication, and the role of a gRNA lariat is not known. Future studies will determine whether these gRNA dynamics represent fundamental features of retroviral biology and whether they occur for other positive-sense RNA viruses.
宿主细胞因子是病毒复制的重要组成部分。人类免疫缺陷病毒 1（HIV-1）是获得性免疫缺陷综合征的逆转录病毒因子，在病毒进入后不久，需要几种宿主因子将病毒基因组 RNA（gRNA）逆转录成 DNA。这些宿主因子之一是 RNA 套索分支酶（Dbr1），它可以切割分支和套索 RNA 的 2'-5' 键。最近的一项研究表明，Dbr1 可以切割 HIV-1 gRNA 套索，这些套索在病毒进入后早期形成。如果没有 Dbr1 的活性，HIV-1 逆转录就会停滞，这与病毒逆转录酶在 gRNA 分支点受阻一致。这些发现与早期对 Ty1 长末端重复逆转录转座子的研究相呼应，Ty1 是一种逆转录病毒模型。目前，病毒 gRNA 的分支和去分支尚未被广泛认为是 HIV-1 复制的特征，gRNA 套索的作用也不清楚。未来的研究将确定这些 gRNA 动力学是否代表逆转录病毒生物学的基本特征，以及它们是否发生在其他正链 RNA 病毒中。
