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

doi:10.1126/science.abb3753

GSTDTAP > 气候变化

DOI	10.1126/science.abb3753
	MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses
	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
	2020-10-09
发表期刊	Science
出版年	2020
英文摘要	A better understanding of cellular mechanisms involved in viral resistance is needed for the next generation of antiviral therapies. Bruchez et al. used a transposon-mediated gene-activation screen to search for previously unreported host restriction factors for Ebola virus (see the Perspective by Wells and Coyne). The authors found that a transcription factor, major histocompatibility complex class II transactivator (CIITA), induces resistance in human cell lines by directing the expression of the p41 isoform of the invariant chain (CD74). CD74 p41 then disrupts cathepsin-mediated Ebola glycoprotein processing, which prevents viral fusion and entry. CD74 p41 can also stymie the endosomal entry of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work should inform future treatments against cathepsin-dependent viruses such as filoviruses and coronaviruses. Additionally, the screening strategy used may serve as a blueprint for uncovering resistance mechanisms against other dangerous pathogens. Science , this issue p. [241][1] see also p. [167][2] Recent outbreaks of Ebola virus (EBOV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have exposed our limited therapeutic options for such diseases and our poor understanding of the cellular mechanisms that block viral infections. Using a transposon-mediated gene-activation screen in human cells, we identify that the major histocompatibility complex (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. 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 they identify an additional function of these proteins beyond their canonical roles in antigen presentation. [1]: /lookup/doi/10.1126/science.abb3753 [2]: /lookup/doi/10.1126/science.abe2977
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/298106
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Anna Bruchez,Ky Sha,Joshua Johnson,et al. MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses[J]. Science,2020.
APA	Anna Bruchez.,Ky Sha.,Joshua Johnson.,Li Chen.,Caroline Stefani.,...&Adam Lacy-Hulbert.(2020).MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.Science.
MLA	Anna Bruchez,et al."MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses".Science (2020).