近日，国际著名杂志Journal of Virology在线刊登了武汉大学生科院吴建国教授研究组的最新研究成果“Activation of the Ras/Raf/MEK pathway facilitates Hepatitis C virus replication via attenuation of the Interferon-JAK-STAT pathway，”，文章中，研究者报导了丙肝病毒逃逸宿主体内抗病毒通路IFN-JAK-STAT的新机制。通讯作者为吴建国教授，第一作者为博士生张祺。
目前全球有两亿人感染丙肝病毒，由它导致的脂肪肝、肝硬化及肝癌严重危害着人类健康。临床上治疗丙肝感染用的是干扰素，但治疗有效率不到50%，说明丙肝病毒有一套逃逸干扰素抗病毒通路的机制。
该研究发现丙肝病毒感染时能激活胞内的Ras/Raf/MEK通路，而此通路的激活会上调干扰素受体IFNAR1的磷酸化水平，加速IFNAR1的降解，最终导致干扰素抗病毒通路IFN-JAK-STAT的功能被削弱。这一发现很好地解释了临床上干扰素治疗丙肝感染有效率偏低的现象，为治疗丙肝感染提供了新的思路与靶标。（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.
