近日,，來自美國喬治亞大學(xué)的研究人員表示,，他們確定了對流感病毒復(fù)制必需的宿主基因及miRNAs,，為流感的治療提供了潛在的新靶點(diǎn)。
甲型流感病毒通過季節(jié)性流行及周期性的大范圍流行,，正嚴(yán)重威脅著人類健康,。一般來說，接種疫苗是降低流感發(fā)病率及致死率的有效途經(jīng),，如果沒有藥物抗性,，藥物預(yù)防的療效也比較顯著。然而,，藥物抗性的迅速出現(xiàn)突出了對新的藥物靶點(diǎn)的迫切需求,。
總所周知，流感病毒的復(fù)制需要一定的宿主細(xì)胞組分,。目前,，對這些宿主細(xì)胞組分的研究已經(jīng)成為了一個新的領(lǐng)域來靶向治療流感。
在這項(xiàng)研究里,，研究人員通過RNA干擾分析,，確定了與流感病毒復(fù)制緊密相關(guān)的人蛋白酶基因。被確定是與流感病毒復(fù)制有關(guān)的基因有ADAMTS7,、CPE,、DPP3、MST1及PRSS12,。進(jìn)一步分析表明,，這些基因主要作用于宿主細(xì)胞內(nèi)控制炎癥(NF-κB),，cAMP/Ca信號(CRE/CREB)及凋亡的細(xì)胞通路。
對控制這些基因表達(dá)的microRNAs的分析表明,，在病毒復(fù)制期間,，宿主細(xì)胞內(nèi)有8種miRNAs調(diào)節(jié)了這些基因的表達(dá)。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0037169
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PMID:
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
