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Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets

Alpha-herpesvirus thymidine kinase (TK) genes are virulence-related genes and are nonessential for viral replication; they are often preferred target genes for the construction of gene-deleted attenuated vaccines and genetically engineered vectors for inserting and expressing foreign genes. The enzy...

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Autores principales: Xie, Ying, Wu, Liping, Wang, Mingshu, Cheng, Anchun, Yang, Qiao, Wu, Ying, Jia, Renyong, Zhu, Dekang, Zhao, XinXin, Chen, Shun, Liu, Mafeng, Zhang, Shaqiu, Wang, Yin, Xu, Zhiwen, Chen, Zhengli, Zhu, Ling, Luo, Qihui, Liu, Yunya, Yu, Yanling, Zhang, Ling, Chen, Xiaoyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517553/
https://www.ncbi.nlm.nih.gov/pubmed/31134006
http://dx.doi.org/10.3389/fmicb.2019.00941
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author Xie, Ying
Wu, Liping
Wang, Mingshu
Cheng, Anchun
Yang, Qiao
Wu, Ying
Jia, Renyong
Zhu, Dekang
Zhao, XinXin
Chen, Shun
Liu, Mafeng
Zhang, Shaqiu
Wang, Yin
Xu, Zhiwen
Chen, Zhengli
Zhu, Ling
Luo, Qihui
Liu, Yunya
Yu, Yanling
Zhang, Ling
Chen, Xiaoyue
author_facet Xie, Ying
Wu, Liping
Wang, Mingshu
Cheng, Anchun
Yang, Qiao
Wu, Ying
Jia, Renyong
Zhu, Dekang
Zhao, XinXin
Chen, Shun
Liu, Mafeng
Zhang, Shaqiu
Wang, Yin
Xu, Zhiwen
Chen, Zhengli
Zhu, Ling
Luo, Qihui
Liu, Yunya
Yu, Yanling
Zhang, Ling
Chen, Xiaoyue
author_sort Xie, Ying
collection PubMed
description Alpha-herpesvirus thymidine kinase (TK) genes are virulence-related genes and are nonessential for viral replication; they are often preferred target genes for the construction of gene-deleted attenuated vaccines and genetically engineered vectors for inserting and expressing foreign genes. The enzymes encoded by TK genes are key kinases in the nucleoside salvage pathway and have significant substrate diversity, especially the herpes simplex virus 1 (HSV-1) TK enzyme, which phosphorylates four nucleosides and various nucleoside analogues. Hence, the HSV-1 TK gene is exploited for the treatment of viral infections, as a suicide gene in antitumor therapy, and even for the regulation of stem cell transplantation and treatment of parasitic infection. This review introduces the effects of α-herpesvirus TK genes on viral virulence and infection in the host and classifies and summarizes the current main application domains and potential uses of these genes. In particular, mechanisms of action, clinical limitations, and antiviral and antitumor therapy development strategies are discussed.
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spelling pubmed-65175532019-05-27 Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets Xie, Ying Wu, Liping Wang, Mingshu Cheng, Anchun Yang, Qiao Wu, Ying Jia, Renyong Zhu, Dekang Zhao, XinXin Chen, Shun Liu, Mafeng Zhang, Shaqiu Wang, Yin Xu, Zhiwen Chen, Zhengli Zhu, Ling Luo, Qihui Liu, Yunya Yu, Yanling Zhang, Ling Chen, Xiaoyue Front Microbiol Microbiology Alpha-herpesvirus thymidine kinase (TK) genes are virulence-related genes and are nonessential for viral replication; they are often preferred target genes for the construction of gene-deleted attenuated vaccines and genetically engineered vectors for inserting and expressing foreign genes. The enzymes encoded by TK genes are key kinases in the nucleoside salvage pathway and have significant substrate diversity, especially the herpes simplex virus 1 (HSV-1) TK enzyme, which phosphorylates four nucleosides and various nucleoside analogues. Hence, the HSV-1 TK gene is exploited for the treatment of viral infections, as a suicide gene in antitumor therapy, and even for the regulation of stem cell transplantation and treatment of parasitic infection. This review introduces the effects of α-herpesvirus TK genes on viral virulence and infection in the host and classifies and summarizes the current main application domains and potential uses of these genes. In particular, mechanisms of action, clinical limitations, and antiviral and antitumor therapy development strategies are discussed. Frontiers Media S.A. 2019-05-08 /pmc/articles/PMC6517553/ /pubmed/31134006 http://dx.doi.org/10.3389/fmicb.2019.00941 Text en Copyright © 2019 Xie, Wu, Wang, Cheng, Yang, Wu, Jia, Zhu, Zhao, Chen, Liu, Zhang, Wang, Xu, Chen, Zhu, Luo, Liu, Yu, Zhang and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Xie, Ying
Wu, Liping
Wang, Mingshu
Cheng, Anchun
Yang, Qiao
Wu, Ying
Jia, Renyong
Zhu, Dekang
Zhao, XinXin
Chen, Shun
Liu, Mafeng
Zhang, Shaqiu
Wang, Yin
Xu, Zhiwen
Chen, Zhengli
Zhu, Ling
Luo, Qihui
Liu, Yunya
Yu, Yanling
Zhang, Ling
Chen, Xiaoyue
Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets
title Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets
title_full Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets
title_fullStr Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets
title_full_unstemmed Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets
title_short Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets
title_sort alpha-herpesvirus thymidine kinase genes mediate viral virulence and are potential therapeutic targets
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517553/
https://www.ncbi.nlm.nih.gov/pubmed/31134006
http://dx.doi.org/10.3389/fmicb.2019.00941
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