Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge

Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge
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DOI:
10.1086/315190
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发表时间:
2000-01-01
影响因子:
6.4
通讯作者:
Huggins, JW
Huggins, JW
中科院分区:
医学2区
文献类型:
--
作者:
Bray, M;Martinez, M;Huggins, JW

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观察西多福韦治疗BALB/c小鼠牛痘病毒感染的疗效,以期在小动物模型上评价治疗强毒正痘病毒感染的新方法。2-5×10(6)pfu的牛痘病毒气雾剂或鼻内注射(Inl)对3-7周龄的动物是致命的,在气雾剂感染的第0、2或4天接种100 mg/kg的西多福韦可使90%-100%的动物存活。第0天的治疗将肺病毒滴度峰值降低了10-100倍,减轻了病毒性肺炎的严重程度,并防止了肺出血。第6~2天的相同剂量对感染INL的小鼠有80%~100%的保护率,而第16~8天或第3~6天的1次接种对INL感染小鼠有部分保护作用。西多福韦延迟但不能阻止合并严重联合免疫缺陷的INL感染小鼠的死亡,用痘苗病毒尾部结痂时的治疗并不阻止疫苗的接种效果。
The efficacy of cidofovir for treatment of cowpox virus infection in BALB/c mice was investigated in an effort to evaluate new therapies for virulent orthopoxvirus infections of the respiratory tract in a small animal model. Exposure to 2-5 x 10(6) pfu of cowpox virus by aerosol or intranasally (inl) was lethal in 3- to 7-week-old animals, One inoculation of 100 mg/kg cidofovir on day 0, 2, or 4, with respect to aerosol infection, resulted in 90%-100% survival. Treatment on day 0 reduced peak pulmonary virus titers 10- to 100-fold, reduced the severity of viral pneumonitis, and prevented pulmonary hemorrhage. The same dose on day -6 to 2 protected 80%-100% of inl infected mice, whereas 1 inoculation on day -16 to -8 or day 3 to 6 was partially protective. Cidofovir delayed but did not prevent the death of inl infected mice with severe combined immunodeficiency, Treatment at the time of tail scarification with vaccinia virus did not block vaccination efficacy.