A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs
A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs
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DOI：
10.1086/511310
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发表时间：
2007-03-01
影响因子：
6.4
通讯作者：
Vasudevan, Subhash G.
中科院分区：
文献类型：
--
作者：
Schul, Wouter;Liu, Wei;Vasudevan, Subhash G.
登革热是一种新出现的虫媒病毒疾病，目前还没有针对这种疾病的疫苗或抗病毒治疗，每年导致数千人死亡。为了开发抗登革热药物的体内测试系统，向缺乏干扰素-α/β和-伽马受体的AG129小鼠注射未适应的登革病毒，导致持续数天的剂量依赖性一过性病毒血症，并在感染后第3天达到峰值。此外，还发现非结构蛋白1，促炎细胞因子水平升高，以及中和IgM和IgG抗体，小鼠出现脾肿大。口服抗病毒化合物7-去氮-2‘-C-甲基-腺苷、N-壬基-脱氧诺吉霉素或6-O-丁酰葡胺以剂量依赖的方式显著减少病毒血症，即使在延迟治疗后也是如此，导致脾肿大和促炎细胞因子水平降低。结果验证了这种登革热病毒血症小鼠模型是测试抗登革热药物的合适系统，并表明在登革热急性期进行抗病毒治疗可以减轻疾病的严重程度。
Dengue fever is an emerging arboviral disease for which no vaccine or antiviral treatment exists and that causes thousands of fatalities each year. To develop an in vivo test system for antidengue drugs, AG129 mice, which are deficient for the interferon-alpha/beta and -gamma receptors, were injected with unadapted dengue virus, resulting in a dose-dependent transient viremia lasting several days and peaking on day 3 after infection. Additionally, nonstructural protein 1, increased levels of proinflammatory cytokines, and neutralizing IgM and IgG antibodies were found, and mice had splenomegaly. Oral administration of the antiviral compounds 7-deaza-2'-C-methyl-adenosine, N-nonyl-deoxynojirimycin, or 6-O-butanoyl castanospermine significantly reduced viremia in a dose-dependent manner, even after delayed treatment, leading to a reduction of splenomegaly and proinflammatory cytokine levels. The results validate this dengue viremia mouse model as a suitable system for testing antidengue drugs and indicate that antiviral treatment during the acute phase of dengue fever can reduce the severity of the disease.