Remesar M C, Blejer J L, Weissenbacher M C, Nejamkis M R
Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
J Med Virol. 1988 Sep;26(1):79-84. doi: 10.1002/jmv.1890260111.
Junin virus, the etiological agent of Argentine hemorrhagic fever, produces in man a disease mainly characterized by hemorrhagic alterations, commonly accompanied by neurological symptoms, and leading to 10% mortality. Intracerebral inoculation in 10-day-old rats or intraperitoneal inoculation in 2-day-old rats leads to high mortality due to severe encephalitis. Here, the effect of Ribavirin on these experimental models was tested in order to evaluate the degree of protection achieved against neuropathological manifestations. In intracerebrally infected 10-day-old rats the drug was administered 2 hr before virus inoculation. Doses ranged from 30 to 90 mg/kg body weight. Protection reached 40% for the 60 and 90 mg doses. Intraperitoneally infected 2-day-old rats received the drug in five 30-mg daily doses, starting the same day as virus inoculation. Survival was 73%. Viral replication within peritoneal macrophages dropped markedly, leading to much lower CNS viral titres. Together with results reported in primates, our findings support further studies on Ribavirin, with a view to eventual trials in humans.
胡宁病毒是阿根廷出血热的病原体,可使人患上一种主要以出血性病变为特征的疾病,通常伴有神经症状,死亡率达10%。对10日龄大鼠进行脑内接种或对2日龄大鼠进行腹腔接种会因严重脑炎导致高死亡率。在此,测试了利巴韦林对这些实验模型的作用,以评估其对神经病理表现的保护程度。在脑内感染的10日龄大鼠中,在病毒接种前2小时给药。剂量范围为30至90毫克/千克体重。60毫克和90毫克剂量的保护率达到40%。腹腔感染的2日龄大鼠从病毒接种当天开始,每天分五次给予30毫克剂量的药物。存活率为73%。腹腔巨噬细胞内的病毒复制明显下降,导致中枢神经系统病毒滴度低得多。与灵长类动物的研究结果一起,我们的发现支持对利巴韦林进行进一步研究,以期最终在人体进行试验。