Activation of the Ras/Raf/MEK Pathway Facilitates HCV Replication via Attenuation of the IFN-JAK-STAT Pathway
作者单位：State Key Laboratory of VirologyCollege of Life SciencesWuhan University
会议名称：《2012年鄂粤微生物学学术年会——湖北省暨武汉微生物学会成立六十年庆祝大会》
会议日期：2012年
学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071005[理学-微生物学] 10[医学]
摘 要：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 *** 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 *** further demonstrated that this effect is regulated through the attenuation of IFN-JAK-STAT *** 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).We also found that the down-regulation of IFNAR1 is caused by the increase in its phosphorylation level stimulated by the activity of Ras/Raf/MEK ***,we observed that HCV infection activates Ras/Raf/MEK ***,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.