登革热在南亚和东南亚、非洲及南美洲很多国家是流行病,在其他地方是一个新出现的威胁。它是由四种登革热病毒(DENV-1、2、3和4)中的其中一种引起的, 由斑蚊传播;目前没有得到批准的疫苗,也没有有效的特效疗法。 登革热病毒是小型黄病毒,很可能需要大量宿主因子才能传播,因此关于这些因子的知识可能会导致潜在药物作用目标及新的媒介控制策略的发现。现在,通过对被DENV-2感染的果蝇细胞采用一种高通量RNAi筛选方法(果蝇与病毒媒介物种相关,较易用基因组学研究工具来操控),研究人员发现了超过100种登革热病毒宿主因子候选对象,它们当中很多在人类细胞中也充当宿主因子。 推荐原始出处: Nature 458, 1047-1050 (23 April 2009) | doi:10.1038/nature07967 Discovery of insect and human dengue virus host factors October M. Sessions1,2, Nicholas J. Barrows2,3,4, Jayme A. Souza-Neto7, Timothy J. Robinson1,5,6, Christine L. Hershey8, Mary A. Rodgers8, Jose L. Ramirez7, George Dimopoulos7, Priscilla L. Yang8, James L. Pearson1,2,3 & Mariano A. Garcia-Blanco1,2,3,9
1 Department of Molecular Genetics and Microbiology, Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection1. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat1, 2. 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 identified3, 4, 5, 6, 7, 8, 9, 10. 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 -glucosidases)3, 4, 5, 7, 9, 10, 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. (责任编辑:Doctor001) |