单纯疱疹病毒1型(herpes simplex virus type 1,HSV-1)是一种能够在各类人群中携带和传播并能引起包括口唇疱疹、荚膜炎、角膜炎和病毒性脑炎等疾病的重要病原体。虽然已有多种类型的HSV-1疫苗处于研发的不同阶段,但仍没有商业化的疫苗...单纯疱疹病毒1型(herpes simplex virus type 1,HSV-1)是一种能够在各类人群中携带和传播并能引起包括口唇疱疹、荚膜炎、角膜炎和病毒性脑炎等疾病的重要病原体。虽然已有多种类型的HSV-1疫苗处于研发的不同阶段,但仍没有商业化的疫苗上市销售。临床上使用的特异性抗HSV-1药物如阿昔洛韦、伐昔洛韦和喷昔洛韦等也面临严重的抗药性威胁,开发新的特异性抗HSV-1药物是当前所面临的主要任务之一。siRNA是一种长度为20~25核苷酸的双链RNA,通过在转录后水平上沉默基因表达发挥干扰作用。siRNA作为一种新的、有潜力的抗病毒药物备受关注,发展也较为迅速。综述近年来siRNA在抗HSV-1方面的研究进展,包括靶向HSV-1关键基因和HSV-1互作的宿主细胞基因的siRNA设计、递送和靶向策略。展开更多
In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic ...In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells.The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR).The results showed that CV-N had a low cytotoxicity on Vero cells with a CC50 of 359.03±0.56 μg/mL,and that it could not directly inactivate HSV-1 infectivity.CV-N not only reduced the CPE of HSV-1 when added before or after viral infection,with a 50% inhibitory concentration (IC50) with 2.26 and 30.16μg/mL respectively,but it also decreased the copies of HSV-1 DNA in infected host cells.The encephalitis model for HSV-1 infection was conducted in Kunming mice,and treated with three dosages of CV-N (0.5,5 & 10 mg/kg) which was administered intraperitoneally at 2h,3d,5d,7d post infection.The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining).Compared with the untreated control group,in the 5mg/kg CV-N and 10mg/kg CV-N treated groups,the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively.HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups,the brain cells did not show visible changes,except for a slight inflammation.Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo,and it would be a promising new candidate for anti-HSV therapeutics.展开更多
文摘单纯疱疹病毒1型(herpes simplex virus type 1,HSV-1)是一种能够在各类人群中携带和传播并能引起包括口唇疱疹、荚膜炎、角膜炎和病毒性脑炎等疾病的重要病原体。虽然已有多种类型的HSV-1疫苗处于研发的不同阶段,但仍没有商业化的疫苗上市销售。临床上使用的特异性抗HSV-1药物如阿昔洛韦、伐昔洛韦和喷昔洛韦等也面临严重的抗药性威胁,开发新的特异性抗HSV-1药物是当前所面临的主要任务之一。siRNA是一种长度为20~25核苷酸的双链RNA,通过在转录后水平上沉默基因表达发挥干扰作用。siRNA作为一种新的、有潜力的抗病毒药物备受关注,发展也较为迅速。综述近年来siRNA在抗HSV-1方面的研究进展,包括靶向HSV-1关键基因和HSV-1互作的宿主细胞基因的siRNA设计、递送和靶向策略。
基金Science and Technology Development Project of Shandong province (2005GG3202068)
文摘In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells.The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR).The results showed that CV-N had a low cytotoxicity on Vero cells with a CC50 of 359.03±0.56 μg/mL,and that it could not directly inactivate HSV-1 infectivity.CV-N not only reduced the CPE of HSV-1 when added before or after viral infection,with a 50% inhibitory concentration (IC50) with 2.26 and 30.16μg/mL respectively,but it also decreased the copies of HSV-1 DNA in infected host cells.The encephalitis model for HSV-1 infection was conducted in Kunming mice,and treated with three dosages of CV-N (0.5,5 & 10 mg/kg) which was administered intraperitoneally at 2h,3d,5d,7d post infection.The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining).Compared with the untreated control group,in the 5mg/kg CV-N and 10mg/kg CV-N treated groups,the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively.HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups,the brain cells did not show visible changes,except for a slight inflammation.Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo,and it would be a promising new candidate for anti-HSV therapeutics.
