2018OncotargetOpen access

Stability and anti-tumor effect of oncolytic herpes simplex virus type 2

Yang Wang, Jing Jin, Zhen Wu, Sheng Hu, Han Hu, Zhifeng Ning, Yanfei Li, Yuting Dong, Jianwen Zou, Zeyong Mao, Xiaotai Shi, Huajun Zheng, Shuang Dong, Fuxing Liu, Zhizheng Fang, Jiliang Wu, Binlei Liu

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Abstract

// Yang Wang 1, * , Jing Jin 1, * , Zhen Wu 1, * , Sheng Hu 2, * , Han Hu 1 , Zhifeng Ning 3 , Yanfei Li 4 , Yuting Dong 5 , Jianwen Zou 4 , Zeyong Mao 5 , Xiaotai Shi 5 , Huajun Zheng 6 , Shuang Dong 2 , Fuxing Liu 3 , Zhizheng Fang 5 , Jiliang Wu 7 and Binlei Liu 1, 4 1 National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, 430068, Hubei, China 2 Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, 430079, Hubei, China 3 Basic Medicine College, Hubei University of Science and Technology, Xianning, 437100, Hubei, China 4 College of Pharmacology, Hubei University of Science and Technology, Xianning, 437100, Hubei, China 5 Wuhan Binhui Biotechnology Co., Ltd., Wuhan, 430075, Hubei, China 6 Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, 201203, Shanghai, China 7 Hubei Provincial Key Laboratory of Cardiocerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning, 437100, Hubei, China * These authors have contributed equally to this work Correspondence to: Binlei Liu, email: 1836035949@qq.com Jiliang Wu, email: xywjl@163.com Keywords: herpes simplex virus type 2; stability; anti-tumor effect Received: August 24, 2017 Accepted: March 22, 2018 Published: May 15, 2018 ABSTRACT Oncolytic virotherapy is a new therapeutic strategy based on the inherent cytotoxicity of viruses and their ability to replicate and spread in tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus type 2 (oHSV-2, named OH2) to treat human cancers, but a systematic evaluation of the stability and oncolytic ability of this virus is lacking. In this study, we evaluated its physical stability, gene modification stability and biological characteristics stability, including its anti-tumor activity in an animal model. The physical characteristics as well as genetic deletions and insertions in OH2 were stable, and the anti-tumor activity remained stable even after passage of the virus for more than 20 generations. In conclusion, OH2 is a virus that has stable structural and biological traits. Furthermore, OH2 is a potent oncolytic agent against tumor cells.

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// Yang Wang 1, * , Jing Jin 1, * , Zhen Wu 1, * , Sheng Hu 2, * , Han Hu 1 , Zhifeng Ning 3 , Yanfei Li 4 , Yuting Dong 5 , Jianwen Zou 4 , Zeyong Mao 5 , Xiaotai Shi 5 , Huajun Zheng 6 , Shuang Dong 2 , Fuxing Liu 3 , Zhizheng Fang 5 , Jiliang Wu 7 and Binlei Liu 1, 4 1 National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, 430068, Hubei, China 2 Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, 430079, Hubei, China 3 Basic Medicine College, Hubei University of Science and Technology, Xianning, 437100, Hubei, China 4 College of Pharmacology, Hubei University of Science and Technology, Xianning, 437100, Hubei, China 5 Wuhan Binhui Biotechnology Co., Ltd., Wuhan, 430075, Hubei, China 6 Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, 201203, Shanghai, China 7 Hubei Provincial Key Laboratory of Cardiocerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning, 437100, Hubei, China * These authors have contributed equally to this work Correspondence to: Binlei Liu, email: 1836035949@qq.com Jiliang Wu, email: xywjl@163.com Keywords: herpes simplex virus type 2; stability; anti-tumor effect Received: August 24, 2017 Accepted: March 22, 2018 Published: May 15, 2018 ABSTRACT Oncolytic virotherapy is a new therapeutic strategy based on the inherent cytotoxicity of viruses and their ability to replicate and spread in tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus type 2 (oHSV-2, named OH2) to treat human cancers, but a systematic evaluation of the stability and oncolytic ability of this virus is lacking. In this study, we evaluated its physical stability, gene modification stability and biological characteristics stability, including its anti-tumor activity in an animal model. The physical characteristics as well as genetic deletions and insertions in OH2 were stable, and the anti-tumor activity remained stable even after passage of the virus for more than 20 generations. In conclusion, OH2 is a virus that has stable structural and biological traits. Furthermore, OH2 is a potent oncolytic agent against tumor cells.

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Available abstract

// Yang Wang 1, * , Jing Jin 1, * , Zhen Wu 1, * , Sheng Hu 2, * , Han Hu 1 , Zhifeng Ning 3 , Yanfei Li 4 , Yuting Dong 5 , Jianwen Zou 4 , Zeyong Mao 5 , Xiaotai Shi 5 , Huajun Zheng 6 , Shuang Dong 2 , Fuxing Liu 3 , Zhizheng Fang 5 , Jiliang Wu 7 and Binlei Liu 1, 4 1 National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, 430068, Hubei, China 2 Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, 430079, Hubei, China 3 Basic Medicine College, Hubei University of Science and Technology, Xianning, 437100, Hubei, China 4 College of Pharmacology, Hubei University of Science and Technology, Xianning, 437100, Hubei, China 5 Wuhan Binhui Biotechnology Co., Ltd., Wuhan, 430075, Hubei, China 6 Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, 201203, Shanghai, China 7 Hubei Provincial Key Laboratory of Cardiocerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning, 437100, Hubei, China * These authors have contributed equally to this work Correspondence to: Binlei Liu, email: 1836035949@qq.com Jiliang Wu, email: xywjl@163.com Keywords: herpes simplex virus type 2; stability; anti-tumor effect Received: August 24, 2017 Accepted: March 22, 2018 Published: May 15, 2018 ABSTRACT Oncolytic virotherapy is a new therapeutic strategy based on the inherent cytotoxicity of viruses and their ability to replicate and spread in tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus type 2 (oHSV-2, named OH2) to treat human cancers, but a systematic evaluation of the stability and oncolytic ability of this virus is lacking. In this study, we evaluated its physical stability, gene modification stability and biological characteristics stability, including its anti-tumor activity in an animal model. The physical characteristics as well as genetic deletions and insertions in OH2 were stable, and the anti-tumor activity remained stable even after passage of the virus for more than 20 generations. In conclusion, OH2 is a virus that has stable structural and biological traits. Furthermore, OH2 is a potent oncolytic agent against tumor cells.

Key concepts: Oncolytic virus, Herpes simplex virus, Virology, Medicine, Cancer research, Virus, Immunology

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