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利巴韦林在克里米亚-刚果出血热病毒(CCHF)感染的体内模型中的疗效。

Ribavirin efficacy in an in vivo model of Crimean-Congo hemorrhagic fever virus (CCHF) infection.

作者信息

Tignor G H, Hanham C A

机构信息

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510.

出版信息

Antiviral Res. 1993 Dec;22(4):309-25. doi: 10.1016/0166-3542(93)90040-p.

Abstract

After intraperitoneal (i.p.) infection of infant mice with CCHF virus, virus titers in liver remained significantly higher than in other organs except blood (serum). Within the liver, virus antigen was first found by immunofluorescence (IFA) in Kupffer cells followed by more extensive hepatic spread. Later, virus was found in other organs including brain and heart. Ribavirin treatment significantly reduced infant mouse mortality and extended the geometric mean time to death. Ribavirin treatment reduced CCHF virus growth in liver and significantly decreased, but did not prevent, viremia. Despite a substantial viremia, infection of other organs including brain and heart was not detected in ribavirin-treated mice. A hepatotropic virus subpopulation with less neurovirulence than the parent was isolated from liver of ribavirin-treated mice (single dose, 100 mg/kg). After serial passage in placebo-treated mice, the exclusive hepatotropism was lost.

摘要

用克里米亚-刚果出血热病毒腹腔内(i.p.)感染幼鼠后,肝脏中的病毒滴度显著高于除血液(血清)外的其他器官。在肝脏内,通过免疫荧光(IFA)首先在库普弗细胞中发现病毒抗原,随后病毒在肝脏中更广泛地传播。之后,在包括脑和心脏在内的其他器官中发现了病毒。利巴韦林治疗显著降低了幼鼠死亡率,并延长了几何平均死亡时间。利巴韦林治疗抑制了肝脏中克里米亚-刚果出血热病毒的生长,并显著降低了病毒血症,但未能阻止病毒血症的发生。尽管存在大量病毒血症,但在接受利巴韦林治疗的小鼠中未检测到包括脑和心脏在内的其他器官受到感染。从接受利巴韦林治疗的小鼠(单剂量,100 mg/kg)肝脏中分离出一种嗜肝病毒亚群,其神经毒力低于亲本病毒。在接受安慰剂治疗的小鼠中连续传代后,其独特的嗜肝性丧失。

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