Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro
Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro
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DOI：
10.1073/pnas.1212379109
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发表时间：
2012-09-04
影响因子：
11.1
通讯作者：
Rice, Charles M.
中科院分区：
文献类型：
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作者：
Schoggins, John W.;Dorner, Marcus;Rice, Charles M.
登革病毒（DENV）是一种全球性疾病威胁，目前还没有批准的抗病毒药物或疫苗。建立依赖于荧光或发光报告物的最先进的筛选系统可能会加速抗DENV治疗剂的开发。然而，存在相对较少的报告者DENV平台。在这里，我们表明，登革病毒可以基因工程表达的绿色荧光蛋白或萤火虫荧光素酶。报道病毒在体外和体内具有感染性，并且对抗病毒化合物、中和抗体和干扰素敏感。生物发光成像用于跟踪小鼠中DENV感染的动态，并显示病毒主要定位于淋巴和肠道相关组织。通过筛选超过350个IFN刺激的抗病毒活性基因的文库，证明了报告基因DENV的高通量潜力。鉴定了几种抗病毒效应物，它们在两个不同的生命周期步骤中靶向DENV。这些病毒为从候选疫苗验证到抗病毒发现的应用提供了强大的平台。
Dengue virus (DENV) is a global disease threat for which there are no approved antivirals or vaccines. Establishing state-of-the-art screening systems that rely on fluorescent or luminescent reporters may accelerate the development of anti-DENV therapeutics. However, relatively few reporter DENV platforms exist. Here, we show that DENV can be genetically engineered to express a green fluorescent protein or firefly luciferase. Reporter viruses are infectious in vitro and in vivo and are sensitive to antiviral compounds, neutralizing antibodies, and interferons. Bioluminescence imaging was used to follow the dynamics of DENV infection in mice and revealed that the virus localized predominantly to lymphoid and gut-associated tissues. The high-throughput potential of reporter DENV was demonstrated by screening a library of more than 350 IFN-stimulated genes for antiviral activity. Several antiviral effectors were identified, and they targeted DENV at two distinct life cycle steps. These viruses provide a powerful platform for applications ranging from validation of vaccine candidates to antiviral discovery.