Regulated control of virus replication by 4-hydroxytamoxifen-induced splicing

oleh: Zhenghao Zhao, Busen Wang, Shipo Wu, Zhe Zhang, Yi Chen, Jinlong Zhang, Yudong Wang, Danni Zhu, Danni Zhu, Yao Li, Jinghan Xu, Lihua Hou, Wei Chen

Format: Article
Diterbitkan: Frontiers Media S.A. 2023-03-01

Deskripsi

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.