Generation of Premature Termination Codon (PTC)-Harboring Pseudorabies Virus (PRV) via Genetic Code Expansion Technology.

Bibliographic Details
Title: Generation of Premature Termination Codon (PTC)-Harboring Pseudorabies Virus (PRV) via Genetic Code Expansion Technology.
Authors: Wang, Tong-Yun1 (AUTHOR) sdndwty@163.com, Sang, Guo-Ju2 (AUTHOR) 18438615167@139.com, Wang, Qian1 (AUTHOR) wangqian@caas.cn, Leng, Chao-Liang3 (AUTHOR) lenghan1223@126.com, Tian, Zhi-Jun1 (AUTHOR) tianzhijun@caas.cn, Peng, Jin-Mei1 (AUTHOR) pengjinmei@caas.cn, Wang, Shu-Jie1 (AUTHOR) wangshujie@caas.cn, Sun, Ming-Xia1 (AUTHOR) sunmingxia@caas.cn, Meng, Fan-Dan1 (AUTHOR) mengfandan@caas.cn, Zheng, Hao2 (AUTHOR) haozheng@shvri.ac.cn, Cai, Xue-Hui1 (AUTHOR) haozheng@shvri.ac.cn, Tang, Yan-Dong1 (AUTHOR) haozheng@shvri.ac.cn
Source: Viruses (1999-4915). Mar2022, Vol. 14 Issue 3, p572-572. 12p.
Subject Terms: *GENETIC code, *AUJESZKY'S disease virus, *ORTHOGONAL systems, *AUTOMATIC control systems, *VACCINE effectiveness, *TRANSFER RNA
Abstract: Despite many efforts and diverse approaches, developing an effective herpesvirus vaccine remains a great challenge. Traditional inactivated and live-attenuated vaccines always raise efficacy or safety concerns. This study used Pseudorabies virus (PRV), a swine herpes virus, as a model. We attempted to develop a live but replication-incompetent PRV by genetic code expansion (GCE) technology. Premature termination codon (PTC) harboring PRV was successfully rescued in the presence of orthogonal system MbpylRS/tRNAPyl pair and unnatural amino acids (UAA). However, UAA incorporating efficacy seemed extremely low in our engineered PRV PTC virus. Furthermore, we failed to establish a stable transgenic cell line containing orthogonal translation machinery for PTC virus replication, and we demonstrated that orthogonal tRNAPyl is a key limiting factor. This study is the first to demonstrate that orthogonal translation system-mediated amber codon suppression strategy could precisely control PRV-PTC engineered virus replication. To our knowledge, this is the first reported PTC herpesvirus generated by GCE technology. Our work provides a proof-of-concept for generating UAAs-controlled PRV-PTC virus, which can be used as a safe and effective vaccine. [ABSTRACT FROM AUTHOR]
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ISSN:19994915
DOI:10.3390/v14030572
Published in:Viruses (1999-4915)
Language:English