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Assessment of the efficacy of the neuraminidase inhibitor oseltamivir against 2009 pandemic H1N1 influenza virus in ferrets.

机译:评估神经氨酸酶抑制剂奥司他韦对雪貂2009年大流行H1N1流感病毒的疗效。

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Pandemic 2009 influenza A (H1N1) virus (H1N1pdm) is different from contemporary seasonal human viruses in that it can cause infection deep in the lungs of critical care patients. Here we establish a mammalian animal model and assessed the efficacy of the neuraminidase (NA) inhibitor oseltamivir treatment against H1N1pdm virus infection. Oseltamivir (25 mg/kg/day twice daily for 5 days) was orally administered to groups of ferrets, starting either 2 or 24 h after inoculation with 10(6)PFU of A/California/04/2009 (H1N1) influenza virus. We determined that virus replication was restricted to 1 or 2 of 4 lung lobes in oseltamivir-treated animals, while virus was consistently isolated from 4 of 4 lung lobes in control animals (1.5-3.8log(10)PFU/g). Analysis of arterial blood oxygenation revealed less pronounced changes in partial oxygen and carbon dioxide pressure in oseltamivir-treated ferrets, and histologic examination confirmed reduced pneumonia. Treated animals had significantly decreased inflammatory responses in the upper respiratory tract (P < 0.05), less fever and weight loss, and less reduction of activity. Virus titers in the nasal washes of treated and control ferrets did not differ significantly. NA sequencing and fluorescence-based phenotypic assays identified no oseltamivir-resistant variants. Overall, oseltamivir treatment decreases the signs of infection and reduced the spread of H1N1pdm influenza virus in the lungs of ferrets and therefore impeded the development of viral pneumonia.
机译:2009年大流行性A型流感(H1N1)病毒(H1N1pdm)与现代季节性人类病毒的不同之处在于,它可以在重症监护患者的肺部深处引起感染。在这里,我们建立了哺乳动物动物模型,并评估了神经氨酸酶(NA)抑制剂奥司他韦治疗H1N1pdm病毒感染的功效。在接种10(6)PFU的A / California / 04/2009(H1N1)流感病毒2或24小时后,向雪貂组口服奥司他韦(25 mg / kg /天,每天两次,共5天)。我们确定病毒的复制仅限于用奥司他韦治疗的动物的4个肺叶中的1个或2个,而病毒始终如一地从对照动物的4个肺叶中的4个中分离出来(1.5-3.8log(10)PFU / g)。分析动脉血氧合后,用奥司他韦治疗的雪貂局部氧分压和二氧化碳压力变化不明显,组织学检查证实肺炎减少。治疗的动物在上呼吸道的炎症反应显着降低(P <0.05),发烧和体重减轻较少,活动减少较少。经处理的雪貂和对照雪貂的鼻洗液中的病毒滴度没有显着差异。 NA测序和基于荧光的表型分析未发现耐奥司他韦的变异。总体而言,奥司他韦治疗可以减少感染的征兆,并减少H1N1pdm流感病毒在雪貂肺中的传播,因此阻碍了病毒性肺炎的发展。

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