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Development of a reverse genetics system for Sosuga virus allows rapid screening of antiviral compounds

机译:Sosuga病毒反向遗传学系统的开发可以快速筛选抗病毒化合物

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摘要

Sosuga virus (SOSV) is a recently discovered zoonotic paramyxovirus isolated from a single human case in 2012; it has been ecologically and epidemiologically associated with transmission by the Egyptian rousette bat (Rousettus aegyptiacus). Bats have long been recognized as sources of novel zoonotic pathogens, including highly lethal paramyxoviruses like Nipah virus (NiV) and Hendra virus (HeV). The ability of SOSV to cause severe human disease supports the need for studies on SOSV pathogenesis to better understand the potential impact of this virus and to identify effective treatments. Here we describe a reverse genetics system for SOSV comprising a minigenome-based assay and a replication-competent infectious recombinant reporter SOSV that expresses the fluorescent protein ZsGreen1 in infected cells. First, we used the minigenome assay to rapidly screen for compounds inhibiting SOSV replication at biosafety level 2 (BSL-2). The antiviral activity of candidate compounds was then tested against authentic viral replication using the reporter SOSV at BSL-3. We identified several compounds with anti-SOSV activity, several of which also inhibit NiV and HeV. Alongside its utility in screening for potential SOSV therapeutics, the reverse genetics system described here is a powerful tool for analyzing mechanisms of SOSV pathogenesis, which will facilitate our understanding of how to combat the potential public health threats posed by emerging bat-borne paramyxoviruses.
机译:Sosuga病毒(SOSV)是一种最近发现的人畜共患副粘病毒,于2012年从一个人的病例中分离出来。它在生态和流行病学上都与埃及轮状蝙蝠(Rousettus aegyptiacus)的传播有关。长期以来,蝙蝠一直被认为是新型人畜共患病原体的来源,包括高度致死的副粘病毒,如尼帕病毒(NiV)和亨德拉病毒(HeV)。 SOSV引起严重人类疾病的能力支持对SOSV发病机理进行研究的需要,以更好地了解这种病毒的潜在影响并确定有效的治疗方法。在这里,我们描述了一种针对SOSV的反向遗传学系统,该系统包括基于微型基因组的检测和具有复制能力的传染性重组报告基因SOSV,其在感染细胞中表达荧光蛋白ZsGreen1。首先,我们使用微型基因组测定法快速筛选了在生物安全等级2(BSL-2)下抑制SOSV复制的化合物。然后使用BSL-3的报告基因SOSV对候选病毒的抗病毒活性进行了抗真实病毒复制的测试。我们鉴定了几种具有抗SOSV活性的化合物,其中一些还可以抑制NiV和HeV。除了可用于筛选潜在的SOSV疗法外,此处描述的反向遗传学系统也是分析SOSV发病机理的强大工具,这将有助于我们理解如何应对新兴的蝙蝠传播的副粘病毒对潜在的公共卫生威胁。

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