近日，國際著名雜志Journal of Virology在線刊登了武漢大學(xué)生科院吳建國教授研究組的最新研究成果“Activation of the Ras/Raf/MEK pathway facilitates Hepatitis C virus replication via attenuation of the Interferon-JAK-STAT pathway,，”,，文章中，研究者報(bào)導(dǎo)了丙肝病毒逃逸宿主體內(nèi)抗病毒通路IFN-JAK-STAT的新機(jī)制,。通訊作者為吳建國教授,，第一作者為博士生張祺。
目前全球有兩億人感染丙肝病毒,，由它導(dǎo)致的脂肪肝,、肝硬化及肝癌嚴(yán)重危害著人類健康。臨床上治療丙肝感染用的是干擾素，但治療有效率不到50%,，說明丙肝病毒有一套逃逸干擾素抗病毒通路的機(jī)制,。
該研究發(fā)現(xiàn)丙肝病毒感染時(shí)能激活胞內(nèi)的Ras/Raf/MEK通路，而此通路的激活會(huì)上調(diào)干擾素受體IFNAR1的磷酸化水平,，加速IFNAR1的降解,，最終導(dǎo)致干擾素抗病毒通路IFN-JAK-STAT的功能被削弱。這一發(fā)現(xiàn)很好地解釋了臨床上干擾素治療丙肝感染有效率偏低的現(xiàn)象,，為治療丙肝感染提供了新的思路與靶標(biāo),。（生物谷Bioon.com）
doi:10.1128/JVI.00688-11
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Activation of the Ras/Raf/MEK pathway facilitates HCV replication via attenuation of the IFN-JAK-STAT pathway
Qi Zhang1,2, Rui Gong1,2, Jing Qu1,2, Yijing Zhou1, Weiyong Liu1, Mingzhou Chen1, Yingle Liu1,2, Ying Zhu1,2 and Jianguo Wu1,2,*
Hepatitis C virus (HCV) is a major cause of chronic liver diseases worldwide, often leading to the development of hepatocellular carcinoma (HCC). Constitutive activation of Ras/Raf/MEK pathway is responsible for approximately 30% of cancers. Here, we attempted to address the correlation between activation of this pathway and HCV replication. We showed that knock-down of Raf1 inhibits HCV replication, while activation of Ras/Raf/MEK pathway by V12, a constitutively active form of Ras, stimulates HCV replication. We further demonstrated that this effect is regulated through the attenuation of IFN-JAK-STAT pathway. Activation of Ras/Raf/MEK pathway down-regulates the expression of IFN-stimulated gene (ISG), attenuates the phosphorylation of STAT1/2, and inhibits the expression of interferon (alpha, beta and omega) receptor 1 and 2 (IFNAR1/2). Furthermore, we observed that HCV infection activates Ras/Raf/MEK pathway. Thus, we propose that during HCV infection, Ras/Raf/MEK pathway is activated, which in turn attenuates IFN-JAK-STAT pathway, resulting in stimulating HCV replication.
