An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancer
Oncolytic virus therapy is a rapidly developing cancer treatment method. The development of oncolytic viruses often involves genetic modifications, such as increased expression of foreign proteins for enhancing the antitumor capabilities and knocking out of virulence loci for improving the safety. T...
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Oncology |
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| author | Lifang Song Bopei Cui Qiushuang Gao Chaoying Hu Qian wang Jialu Zhang Yajing Li Guanxing Liu Yulong Fu Ying Wang Kelei Li Xiaotian Hao Fan Gao Xing Wu Qunying Mao Zhenglun Liang Yongxin Yu |
| author_facet | Lifang Song Bopei Cui Qiushuang Gao Chaoying Hu Qian wang Jialu Zhang Yajing Li Guanxing Liu Yulong Fu Ying Wang Kelei Li Xiaotian Hao Fan Gao Xing Wu Qunying Mao Zhenglun Liang Yongxin Yu |
| author_sort | Lifang Song |
| collection | DOAJ |
| description | Oncolytic virus therapy is a rapidly developing cancer treatment method. The development of oncolytic viruses often involves genetic modifications, such as increased expression of foreign proteins for enhancing the antitumor capabilities and knocking out of virulence loci for improving the safety. The wild-type coxsackievirus B5 (CV-B5/F) exhibits potent antitumor activity against non-small cell lung cancer. However, CV-B5 poses pathogenic risks to infants and young children, warranting further virulence attenuation to develop a safe strain. No attenuating locus has been reported for CV-B5. In this study, we attenuated the original strain CV-B5/F by low-temperature passage for 30 generations and identified the virulence locus N157K in the structural protein VP1 using reverse genetics analysis. The attenuated strain carrying VP1-N157K retained the antitumor capabilities as the original strain. In addition, an exploration of the potential attenuation mechanisms revealed that the VP1-N157K mutation site weakened the replication ability of CV-B5. In summary, we identified a key virulence locus of CV-B5 and constructed an attenuated strain, which retains the oncolytic activity of the wild-type strain against non-small cell lung cancer with increased safety. |
| format | Article |
| id | doaj-art-c5f21740e0224c2181cadff0fb4582b8 |
| institution | Matheson Library |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-c5f21740e0224c2181cadff0fb4582b82025-06-27T05:53:08ZengElsevierMolecular Therapy: Oncology2950-32992025-09-01333200999An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancerLifang Song0Bopei Cui1Qiushuang Gao2Chaoying Hu3Qian wang4Jialu Zhang5Yajing Li6Guanxing Liu7Yulong Fu8Ying Wang9Kelei Li10Xiaotian Hao11Fan Gao12Xing Wu13Qunying Mao14Zhenglun Liang15Yongxin Yu16Division of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; National Engineering Technology Research Center for Combined Vaccines, Wuhan 430207, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; College of Integrative Medicine, Hebei University of Chinese Medicine, Hebei 050200, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; Shanghai Institute of Biological Products Co., Ltd, Shanghai 201209, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; Changchun Institute of Biological Products Co., Ltd, Changchun 130012, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; Beijing Minhai Biotechnology Co., Ltd, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, ChinaDivision of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; Corresponding author: Qunying Mao, Division of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China.Division of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; Corresponding author: Zhenglun Liang, Division of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China.Division of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China; National Engineering Technology Research Center for Combined Vaccines, Wuhan 430207, China; Corresponding author: Yongxin Yu, Division of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, Beijing 102629, China.Oncolytic virus therapy is a rapidly developing cancer treatment method. The development of oncolytic viruses often involves genetic modifications, such as increased expression of foreign proteins for enhancing the antitumor capabilities and knocking out of virulence loci for improving the safety. The wild-type coxsackievirus B5 (CV-B5/F) exhibits potent antitumor activity against non-small cell lung cancer. However, CV-B5 poses pathogenic risks to infants and young children, warranting further virulence attenuation to develop a safe strain. No attenuating locus has been reported for CV-B5. In this study, we attenuated the original strain CV-B5/F by low-temperature passage for 30 generations and identified the virulence locus N157K in the structural protein VP1 using reverse genetics analysis. The attenuated strain carrying VP1-N157K retained the antitumor capabilities as the original strain. In addition, an exploration of the potential attenuation mechanisms revealed that the VP1-N157K mutation site weakened the replication ability of CV-B5. In summary, we identified a key virulence locus of CV-B5 and constructed an attenuated strain, which retains the oncolytic activity of the wild-type strain against non-small cell lung cancer with increased safety.http://www.sciencedirect.com/science/article/pii/S2950329925000682MT: Regular Issueoncolytic virusreverse geneticsvirulencesafetycoxsackievirus |
| spellingShingle | Lifang Song Bopei Cui Qiushuang Gao Chaoying Hu Qian wang Jialu Zhang Yajing Li Guanxing Liu Yulong Fu Ying Wang Kelei Li Xiaotian Hao Fan Gao Xing Wu Qunying Mao Zhenglun Liang Yongxin Yu An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancer Molecular Therapy: Oncology MT: Regular Issue oncolytic virus reverse genetics virulence safety coxsackievirus |
| title | An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancer |
| title_full | An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancer |
| title_fullStr | An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancer |
| title_full_unstemmed | An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancer |
| title_short | An attenuated coxsackievirus B5 mutant carrying VP1-N157K retains oncolytic potency against non-small cell lung cancer |
| title_sort | attenuated coxsackievirus b5 mutant carrying vp1 n157k retains oncolytic potency against non small cell lung cancer |
| topic | MT: Regular Issue oncolytic virus reverse genetics virulence safety coxsackievirus |
| url | http://www.sciencedirect.com/science/article/pii/S2950329925000682 |
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