RNAi screening reveals requirement for host cell secretory pathway in infection by diverse families of negative-strand RNA viruses
RNAi screening reveals requirement for host cell secretory pathway in infection by diverse families of negative-strand RNA viruses
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DOI：
10.1073/pnas.1113643108
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发表时间：
2011-11-22
影响因子：
11.1
通讯作者：
Pattnaik, Asit K.
中科院分区：
文献类型：
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作者：
Panda, Debasis;Das, Anshuman;Pattnaik, Asit K.
负链（NS）RNA病毒包括许多在人类和动物中引起严重疾病的病原体。尽管它们的临床重要性，很少有人知道他们的感染所需的宿主因素。我们使用水泡性口炎病毒（VSV）（弹状病毒科的一种原型NS RNA病毒）进行了人类全基因组SiRNA筛选，并鉴定了病毒感染所需的72个宿主基因。这些基因中的许多基因也是其他两种NS RNA病毒感染所必需的，这两种病毒是沙粒病毒科的淋巴细胞性脉络丛脑膜炎病毒和副粘病毒科的人类副流感病毒3型。影响不同阶段的VSV感染，如进入/脱壳，基因表达，和组装/释放的基因进行了鉴定。耗尽的蛋白质的外壳体复合物I或其上游效应ARF 1或GBF 1导致检测到的VSV RNA的水平降低。淋巴细胞性脉络丛脑膜炎病毒和人副流感病毒3型感染也需要Coatomer复合物I。这些结果突出了进化上保守的要求，基因表达的不同家庭的NS RNA病毒，并证明参与宿主细胞分泌途径的过程中。
Negative-strand (NS) RNA viruses comprise many pathogens that cause serious diseases in humans and animals. Despite their clinical importance, little is known about the host factors required for their infection. Using vesicular stomatitis virus (VSV), a prototypic NS RNA virus in the family Rhabdoviridae, we conducted a human genome-wide siRNA screen and identified 72 host genes required for viral infection. Many of these identified genes were also required for infection by two other NS RNA viruses, the lymphocytic choriomeningitis virus of the Arenaviridae family and human parainfluenza virus type 3 of the Paramyxoviridae family. Genes affecting different stages of VSV infection, such as entry/uncoating, gene expression, and assembly/release, were identified. Depletion of the proteins of the coatomer complex I or its upstream effectors ARF1 or GBF1 led to detection of reduced levels of VSV RNA. Coatomer complex I was also required for infection of lymphocytic choriomeningitis virus and human parainfluenza virus type 3. These results highlight the evolutionarily conserved requirements for gene expression of diverse families of NS RNA viruses and demonstrate the involvement of host cell secretory pathway in the process.