Discovery of insect and human dengue virus host factors.
Discovery of insect and human dengue virus host factors.
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DOI：
10.1038/nature07967
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发表时间：
2009-04-23
期刊：
影响因子：
64.8
通讯作者：
Garcia-Blanco, Mariano A.
中科院分区：
文献类型：
--
作者：
Sessions, October M.;Barrows, Nicholas J.;Souza-Neto, Jayme A.;Robinson, Timothy J.;Hershey, Christine L.;Rodgers, Mary A.;Ramirez, Jose L.;Dimopoulos, George;Yang, Priscilla L.;Pearson, James L.;Garcia-Blanco, Mariano A.
登革热（DF）是人类最常见的节肢动物传播的病毒性疾病，几乎有一半的世界人口处于感染的危险之中。高患病率，缺乏有效的疫苗，缺乏特异性治疗，使DF成为全球公共卫生威胁。鉴于其紧凑的基因组，登革病毒（DENV 1-4）和其他黄病毒可能需要大量的宿主因子;然而，仅鉴定了有限数量的人类和甚至更少数量的昆虫宿主因子。为了发现DENV-2繁殖所需的昆虫宿主因子，我们使用完善的22，632 dsRNA文库在果蝇细胞中进行了全基因组RNA干扰筛选。该筛选鉴定了116种候选登革病毒宿主因子（DVHF）（补充图1）。虽然有些以前与黄病毒有关（例如，V-ATP酶和α-葡糖苷酶），大多数DVHF新涉及DENV繁殖。双翅目DVHF有82个容易识别的人类同源物，使用靶向siRNA筛选，我们发现其中42个是人类DVHF。这表明双翅目昆虫和人类宿主之间所需因子的显著保守性。这项工作提出了控制昆虫载体和哺乳动物宿主感染的新方法。
Dengue fever (DF) 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 DF a global public health threat. Given their compact genomes, dengue viruses (DENV 1-4) and other flaviviruses likely 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. To discover insect host factors required for DENV-2 propagation, we carried out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 dsRNA library. This screen identified 116 candidate dengue virus host factors (DVHFs) (Supplementary Fig. 1). While some were previously associated with flaviviruses (e.g., V-ATPases and alpha-glucosidases), most DVHFs were newly implicated in DENV propagation. The dipteran DVHFs had eighty-two readily recognizable human homologues and, using a targeted siRNA screen, we showed that forty-two of these are human DVHFs. This indicates remarkable conservation of required factors between dipteran and human hosts. This work suggests novel approaches to control infection in the insect vector and the mammalian host.
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作者：
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DOI：
10.1073/pnas.0703348104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Emara, Mohamed M.;Brinton, Margo A.
通讯作者：
Brinton, Margo A.