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MHC II反式激活因子CIITA诱导细胞对埃博拉病毒和SARS样冠状病毒的抗药性
作者:小柯机器人 发布时间:2020/8/28 22:45:02

美国Benaroya研究所Adam Lacy-Hulbert团队发现,MHC II反式激活因子CIITA诱导细胞对埃博拉病毒和SARS样冠状病毒的抗性。2020年8月27日,《科学》在线发表了这一成果。

通过在人类细胞中使用转座子介导的基因激活筛选,研究人员确定了MHC II反式激活因子(CIITA)具有针对埃博拉病毒(EBOV)的抗病毒活性。CIITA通过激活恒定链CD74的p41亚型表达来诱导抗性,进而通过阻止组织蛋白酶介导的埃博拉糖蛋白(EboGP)加工来抑制病毒进入。
 
研究人员进一步表明CD74 p41可以阻断包括SARS-CoV-2在内的冠状病毒內吞体进入途径。因此,这些数据暗示了CIITA和CD74参与宿主对多种病毒的防御,并确定了这些蛋白质在抗原呈递中经典作用之外的其他功能。
 
据悉,最近爆发的EBOV和SARS-CoV-2暴露了人类有限的治疗选择以及对阻止病毒感染的细胞机制了解不足。 
 
附:英文原文

Title: MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses

Author: Anna Bruchez, Ky Sha, Joshua Johnson, Li Chen, Caroline Stefani, Hannah McConnell, Lea Gaucherand, Rachel Prins, Kenneth A. Matreyek, Adam J. Hume, Elke Mühlberger, Emmett V. Schmidt, Gene G. Olinger, Lynda M. Stuart, Adam Lacy-Hulbert

Issue&Volume: 2020/08/27

Abstract: Abstract Recent outbreaks of Ebola virus (EBOV) and SARS-CoV-2 have exposed our limited therapeutic options and poor understanding of cellular mechanisms that block viral infections. Using a transposon-mediated gene-activation screen in human cells, we identify that the MHC class II transactivator (CIITA) has antiviral activity against EBOV. CIITA induces resistance by activating expression of the p41 isoform of invariant chain CD74, which inhibits viral entry by blocking cathepsin-mediated processing of the Ebola glycoprotein (EboGP). We further show that CD74 p41 can block the endosomal entry pathway of coronaviruses, including SARS-CoV-2. These data therefore implicate CIITA and CD74 in host defense against a range of viruses, and identify an additional function of these proteins beyond their canonical roles in antigen presentation.

DOI: 10.1126/science.abb3753

Source: https://science.sciencemag.org/content/early/2020/08/26/science.abb3753

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037