白细胞介素-12基因治疗急性感染单纯疱疹病毒小鼠实验研究

Intravascular interleukin-12 gene therapy exhibits potent antiviral activity against acute herpes simplex virus infection in mice

[目的]探讨经静脉转染表达mIL-12的DNA质粒对小鼠1型单纯疱疹病毒(HSV-1)急性感染的预防和治疗作用.[方法]经腹腔接种HSV-1建立小鼠模型,用水流动力学方法将mIL-12基因转染Balb/c小鼠,比较观察实验组与对照组生存率,用ELISA法检测血清中细胞因子水平,用小鼠脾细胞评价细胞毒T细胞(CTL)和淋巴细胞增殖反应.[结果]与对照组比较,转染pGEG.mIL-12组小鼠生存率明显提高,血清中白细胞介素12(IL-12)及γ干扰素(IFN-γ)质量浓度明显升高,脾淋巴细胞增殖反应明显增强,而对特异性P815.gB细胞的CTL水平未见提高.[结论]用水流动力学方法转染小鼠IL-12基因对小鼠HSV-1急性感染有预防和治疗作用.

OBJECTIVE To explore the treatment and prophylactic of acute herpes simplex virus type 1（HSV-1） infection efficacy of intravascular administration of plasmid DNA expressing mIL-12 in mice.METHODSTo establish HSV-1 infection models,mice were injected with viral suspension into the peritoneal cavity.The hydrodynamics based transfection was performed for transferring the pGEG.mIL-12 into Balb/c mice.The different survival rate was observed in experimental and control groups.The expression of interleukin-12（IL-12） and IFN-γ were assayed by ELISA,and CTL and lymphocyte proliferation from the spleen cells were measured.RESULTSCompared with mice in control group,resulting in significant prolongation of survival period of the mice,the significant elevation of the serum concentration of IL-12 and IFN-γ were detected in mice treated with pGEG.mIL-12.Lymphocyte proliferation was significantly elevated in these mice,but failed to elicit CTL activity at detectable level.CONCLUSIONIntravascular immunization of IL-12 gene has an advantage in preventing and treating the acute infection with HSV-1 in mice.