Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategies

Parvovirus is comprised of a single-stranded DNA structure, encompassing distinct structural and non-structural proteins. Structural proteins are referred as viral proteins, which facilitate for the viral capsid. Among non-structural proteins, NS1 is the most significant, exhibiting substantial char...

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Main Authors: Abdul Haseeb, Wafa Yousaf, Zhigang Cao, Kuohai Fan, Na Sun, Panpan Sun, Yaogui Sun, Huizhen Yang, Wei Yin, Hua Zhang, Zhenbiao Zhang, Jia Zhong, Jianzhong Wang, Hongquan Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1631433/full
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author Abdul Haseeb
Wafa Yousaf
Zhigang Cao
Kuohai Fan
Kuohai Fan
Na Sun
Panpan Sun
Yaogui Sun
Huizhen Yang
Wei Yin
Hua Zhang
Zhenbiao Zhang
Jia Zhong
Jianzhong Wang
Hongquan Li
author_facet Abdul Haseeb
Wafa Yousaf
Zhigang Cao
Kuohai Fan
Kuohai Fan
Na Sun
Panpan Sun
Yaogui Sun
Huizhen Yang
Wei Yin
Hua Zhang
Zhenbiao Zhang
Jia Zhong
Jianzhong Wang
Hongquan Li
author_sort Abdul Haseeb
collection DOAJ
description Parvovirus is comprised of a single-stranded DNA structure, encompassing distinct structural and non-structural proteins. Structural proteins are referred as viral proteins, which facilitate for the viral capsid. Among non-structural proteins, NS1 is the most significant, exhibiting substantial characteristics related to viral replication, pathogenicity, and is notably recognized for its remarkable oncolytic properties. NS1 possesses a distinctive structure; however, it differs across different parvovirus species. It is comprised of three fundamental domains: the N-terminal origin binding, helicase domain, and C-terminal domain, all crucial for significant functions. In several parvovirus species, such as CPV, MVM, BPV, and HPV-B19, NS1 halts the cell cycle at distinct stages, including G1, G2, and S phases of the life cycle, and induces cell death. Predominantly, parvovirus NS1 has also been significantly recognized to induce tumor cell death in vitro and in vivo by following different mechanisms, including cytotoxicity, autophagy, immunomodulation, mitochondrial depolarization, and most significantly, apoptosis. This may lead to several intracellular changes, including reactive oxygen species (ROS) level, mitochondria, PARP, caspase, and their subtype activation, ultimately leading to DNA and other cellular level changes, which facilitate apoptotic cell death. These characteristics of NS1 and its combinational therapy revealed a wide range of evidential research that demonstrated its anti-tumor effects through several pathways and can even induce a substantial activation of the immune response. This review mainly aims to elucidate the oncolytic attributes of parvoviral NS1, focusing on its capabilities and the mechanism demonstrated in prior research. It also addresses genetic engineering and combinational therapy aimed at augmenting the oncolytic efficacy of NS1 for more potent application as a tumor therapeutic agent. The increasing focus on virotherapy and precision oncology underscores the necessity for thorough exploration of the molecular mechanisms, delivery techniques, and clinical implications of NS1, thereby facilitating the development of innovative, tumor-selective anticancer approaches.
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spelling doaj-art-a7e8aebc47c8448ebbbff5632dbae9d22025-08-20T03:39:26ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-08-011610.3389/fmicb.2025.16314331631433Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategiesAbdul Haseeb0Wafa Yousaf1Zhigang Cao2Kuohai Fan3Kuohai Fan4Na Sun5Panpan Sun6Yaogui Sun7Huizhen Yang8Wei Yin9Hua Zhang10Zhenbiao Zhang11Jia Zhong12Jianzhong Wang13Hongquan Li14Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaLaboratory Animal Center, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, ChinaParvovirus is comprised of a single-stranded DNA structure, encompassing distinct structural and non-structural proteins. Structural proteins are referred as viral proteins, which facilitate for the viral capsid. Among non-structural proteins, NS1 is the most significant, exhibiting substantial characteristics related to viral replication, pathogenicity, and is notably recognized for its remarkable oncolytic properties. NS1 possesses a distinctive structure; however, it differs across different parvovirus species. It is comprised of three fundamental domains: the N-terminal origin binding, helicase domain, and C-terminal domain, all crucial for significant functions. In several parvovirus species, such as CPV, MVM, BPV, and HPV-B19, NS1 halts the cell cycle at distinct stages, including G1, G2, and S phases of the life cycle, and induces cell death. Predominantly, parvovirus NS1 has also been significantly recognized to induce tumor cell death in vitro and in vivo by following different mechanisms, including cytotoxicity, autophagy, immunomodulation, mitochondrial depolarization, and most significantly, apoptosis. This may lead to several intracellular changes, including reactive oxygen species (ROS) level, mitochondria, PARP, caspase, and their subtype activation, ultimately leading to DNA and other cellular level changes, which facilitate apoptotic cell death. These characteristics of NS1 and its combinational therapy revealed a wide range of evidential research that demonstrated its anti-tumor effects through several pathways and can even induce a substantial activation of the immune response. This review mainly aims to elucidate the oncolytic attributes of parvoviral NS1, focusing on its capabilities and the mechanism demonstrated in prior research. It also addresses genetic engineering and combinational therapy aimed at augmenting the oncolytic efficacy of NS1 for more potent application as a tumor therapeutic agent. The increasing focus on virotherapy and precision oncology underscores the necessity for thorough exploration of the molecular mechanisms, delivery techniques, and clinical implications of NS1, thereby facilitating the development of innovative, tumor-selective anticancer approaches.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1631433/fullparvovirusesNS1cell cycle arrestapoptosisoncolysisimmunomodulation
spellingShingle Abdul Haseeb
Wafa Yousaf
Zhigang Cao
Kuohai Fan
Kuohai Fan
Na Sun
Panpan Sun
Yaogui Sun
Huizhen Yang
Wei Yin
Hua Zhang
Zhenbiao Zhang
Jia Zhong
Jianzhong Wang
Hongquan Li
Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategies
Frontiers in Microbiology
parvoviruses
NS1
cell cycle arrest
apoptosis
oncolysis
immunomodulation
title Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategies
title_full Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategies
title_fullStr Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategies
title_full_unstemmed Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategies
title_short Parvoviruses NS1 oncolytic attributes: mechanistic insights and synergistic anti-tumor therapeutic strategies
title_sort parvoviruses ns1 oncolytic attributes mechanistic insights and synergistic anti tumor therapeutic strategies
topic parvoviruses
NS1
cell cycle arrest
apoptosis
oncolysis
immunomodulation
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1631433/full
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