Oncolytic virus therapy is a promising strategy for cancer treatment.Herpes simplex virus type 1(HSV-1)has been successfully used in oncolytic virotherapy.In the present research,we applied an HSV-1 synthetic genomics...Oncolytic virus therapy is a promising strategy for cancer treatment.Herpes simplex virus type 1(HSV-1)has been successfully used in oncolytic virotherapy.In the present research,we applied an HSV-1 synthetic genomics platform to construct two oncolytic viruses,oHSV-1.1 and oHSV-1.2.oHSV-1.1 had the virulence gene ICP34.5 and ICP47 deleted for attenuation,and oHSV-1.2 was additionally armed with murine granulocyte macrophage-colony stimulating factor(GM-CSF)and interleukin-12(IL-12).The oncolytic viruses were evaluated in vitro and in an immunocompetent murine melanoma model.The animal experiments confirmed that both oncolytic viruses displayed antitumor efficacy,including inhibiting tumor growth and prolonging overall survival.Compared with oHSV-1.1,oHSV-1.2 demonstrated superior tumor growth suppression and enhanced antitumor efficacies,as evidenced by increased tumor cell apoptosis,cytotoxic T cells and macrophages infiltration,IFN-γ production,and upregulation of inflammatory-related gene expression.Our research highlights the potential of oncolytic HSV-1 expressing both GM-CSF and IL-12 for melanoma therapy,and provides a promising strategy for further development of oncolytic virotherapy.展开更多
人类单纯疱疹病毒1型(Herpes simplex virus type I,HSV-1)是一种在世界范围内各类人群中广泛携带和传播的重要病原体。HSV-1感染能引起包括口唇疱疹、病毒性角膜炎和病毒性脑炎在内的多种疾病。不论是在HSV-1的裂解感染、潜伏感染或是...人类单纯疱疹病毒1型(Herpes simplex virus type I,HSV-1)是一种在世界范围内各类人群中广泛携带和传播的重要病原体。HSV-1感染能引起包括口唇疱疹、病毒性角膜炎和病毒性脑炎在内的多种疾病。不论是在HSV-1的裂解感染、潜伏感染或是再激活感染过程中,其所编码的蛋白和miRNAs都与宿主细胞因子发生着复杂的相互作用,这些相互作用的结果影响着宿主细胞的生理过程和HSV-1的复制。本文综述了近年来宿主因子在HSV-1复制过程中的调控作用及其机制,为抗HSV-1药物和疫苗研发提供新的思路。展开更多
基金supported by grant from the National Key R&D Program of China(2023YFC2306600)the Hubei Natural Science Foundation for Distinguished Young Scholars(2021CFA050).
文摘Oncolytic virus therapy is a promising strategy for cancer treatment.Herpes simplex virus type 1(HSV-1)has been successfully used in oncolytic virotherapy.In the present research,we applied an HSV-1 synthetic genomics platform to construct two oncolytic viruses,oHSV-1.1 and oHSV-1.2.oHSV-1.1 had the virulence gene ICP34.5 and ICP47 deleted for attenuation,and oHSV-1.2 was additionally armed with murine granulocyte macrophage-colony stimulating factor(GM-CSF)and interleukin-12(IL-12).The oncolytic viruses were evaluated in vitro and in an immunocompetent murine melanoma model.The animal experiments confirmed that both oncolytic viruses displayed antitumor efficacy,including inhibiting tumor growth and prolonging overall survival.Compared with oHSV-1.1,oHSV-1.2 demonstrated superior tumor growth suppression and enhanced antitumor efficacies,as evidenced by increased tumor cell apoptosis,cytotoxic T cells and macrophages infiltration,IFN-γ production,and upregulation of inflammatory-related gene expression.Our research highlights the potential of oncolytic HSV-1 expressing both GM-CSF and IL-12 for melanoma therapy,and provides a promising strategy for further development of oncolytic virotherapy.
文摘人类单纯疱疹病毒1型(Herpes simplex virus type I,HSV-1)是一种在世界范围内各类人群中广泛携带和传播的重要病原体。HSV-1感染能引起包括口唇疱疹、病毒性角膜炎和病毒性脑炎在内的多种疾病。不论是在HSV-1的裂解感染、潜伏感染或是再激活感染过程中,其所编码的蛋白和miRNAs都与宿主细胞因子发生着复杂的相互作用,这些相互作用的结果影响着宿主细胞的生理过程和HSV-1的复制。本文综述了近年来宿主因子在HSV-1复制过程中的调控作用及其机制,为抗HSV-1药物和疫苗研发提供新的思路。
