近日,来自美国乔治亚大学的研究人员表示,他们确定了对流感病毒复制必需的宿主基因及miRNAs,为流感的治疗提供了潜在的新靶点。
甲型流感病毒通过季节性流行及周期性的大范围流行,正严重威胁着人类健康。一般来说,接种疫苗是降低流感发病率及致死率的有效途经,如果没有药物抗性,药物预防的疗效也比较显著。然而,药物抗性的迅速出现突出了对新的药物靶点的迫切需求。
总所周知,流感病毒的复制需要一定的宿主细胞组分。目前,对这些宿主细胞组分的研究已经成为了一个新的领域来靶向治疗流感。
在这项研究里,研究人员通过RNA干扰分析,确定了与流感病毒复制紧密相关的人蛋白酶基因。被确定是与流感病毒复制有关的基因有ADAMTS7、CPE、DPP3、MST1及PRSS12。进一步分析表明,这些基因主要作用于宿主细胞内控制炎症(NF-κB),cAMP/Ca信号(CRE/CREB)及凋亡的细胞通路。
对控制这些基因表达的microRNAs的分析表明,在病毒复制期间,宿主细胞内有8种miRNAs调节了这些基因的表达。(生物谷Deepblue编译)
doi: 10.1371/journal.pone.0037169
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MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication
Victoria A. Meliopoulos, Lauren E. Andersen, Paula Brooks, Xiuzhen Yan, Abhijeet Bakre, J. Keegan Coleman, S. Mark Tompkins, Ralph A. Tripp.
Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines.However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention.In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis.Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies