Tweet
Science 27 Aug 2020:
eabb3753
DOI: 10.1126/science.abb3753
Anna Bruchez1,*,†, Ky Sha1,*,Joshua Johnson2,‡, Li Chen3, Caroline Stefani1, Hannah McConnell1,?, Lea Gaucherand1,?, Rachel Prins1, Kenneth A. Matreyek4,†, Adam J. Hume5,6, Elke M?hlberger5,6, Emmett V. Schmidt7, Gene G. Olinger2,5,6,8, Lynda M. Stuart1,9, Adam Lacy-Hulbert1,10,#
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.
https://science.sciencemag.org/conte...cience.abb3753
eabb3753
DOI: 10.1126/science.abb3753
Anna Bruchez1,*,†, Ky Sha1,*,Joshua Johnson2,‡, Li Chen3, Caroline Stefani1, Hannah McConnell1,?, Lea Gaucherand1,?, Rachel Prins1, Kenneth A. Matreyek4,†, Adam J. Hume5,6, Elke M?hlberger5,6, Emmett V. Schmidt7, Gene G. Olinger2,5,6,8, Lynda M. Stuart1,9, Adam Lacy-Hulbert1,10,#
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.
https://science.sciencemag.org/conte...cience.abb3753