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Discovery Of Insect And Human Dengue Virus Host Factors

机译：发现昆虫和人类登革热病毒宿主因子

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Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and a-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.
机译：登革热是人类中最常见的节肢动物传播的病毒性疾病，全世界近一半的人口有感染的风险。高患病率，缺乏有效疫苗以及缺乏特殊治疗共同导致登革热成为全球公共卫生威胁。鉴于其紧凑的基因组，登革热病毒（DENV-1-4）和其他黄病毒可能需要大量宿主因子。然而，仅确定了有限数量的人类，甚至更少的昆虫宿主因子。在这里，我们通过使用成熟的22,632双链RNA库在果蝇细胞中进行全基因组RNA干扰筛选，确定了DENV-2繁殖所需的昆虫宿主因子。此屏幕确定了116个候选登革热病毒宿主因子（DVHF）。尽管有些病毒以前与黄病毒有关（例如V-ATPase和α-葡萄糖苷酶），但大多数DVHF都与登革热病毒的传播有关。敌百虫DVHFs具有82个易于识别的人类同源物，使用定向短干扰RNA筛选，我们显示其中42个是人类DVHFs。这表明二萜和人类宿主之间所需因子的显着保守。这项工作提出了控制昆虫媒介和哺乳动物宿主感染的新方法。

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