水泡性口炎病毒
英特因
生物
RNA剪接
病毒复制
RNA病毒
核糖核酸
病毒学
聚合酶
弹状病毒科
病毒
细胞生物学
遗传学
DNA
基因
作者
Zeyao Zhao,Busen Wang,Shipo Wu,Zhe Zhang,Yi Chen,Jinlong Zhang,Yudong Wang,Daling Zhu,Yao Li,Jinzhang Xu,Lihua Hou,Wei Chen
标识
DOI:10.3389/fmicb.2023.1112580
摘要
Designing a modified virus that can be controlled to replicate will facilitate the study of pathogenic mechanisms of virus and virus-host interactions. Here, we report a universal switch element that enables precise control of virus replication after exposure to a small molecule. Inteins mediate a traceless protein splicing-ligation process, and we generate a series of modified vesicular stomatitis virus (VSV) with intein insertion into the nucleocapsid, phosphoprotein, or large RNA-dependent RNA polymerase of VSV. Two recombinant VSV, LC599 and LY1744, were screened for intein insertion in the large RNA-dependent RNA polymerase of VSV, and their replication was regulated in a dose-dependent manner with the small molecule 4-hydroxytamoxifen, which induces intein splicing to restore the VSV replication. Furthermore, in the presence of 4-hydroxytamoxifen, the intein-modified VSV LC599 replicated efficiently in an animal model like a prototype of VSV. Thus, we present a simple and highly adaptable tool for regulating virus replication.
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