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

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalScience
Volume370
Issue number6513
DOIs
StatePublished - Oct 9 2020
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'MHC class II transactivator CIITA induces cell resistance to ebola virus and SARS-like coronaviruses'. Together they form a unique fingerprint.

Cite this