2. Academic Validation
  3. MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses

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

  • Science. 2020 Oct 9;370(6513):241-247. doi: 10.1126/science.abb3753.
Anna Bruchez # 1,  Ky Sha # 1,  Joshua Johnson 2,  Li Chen 3,  Caroline Stefani 1,  Hannah McConnell 1,  Lea Gaucherand 1,  Rachel Prins 1,  Kenneth A Matreyek 4,  Adam J Hume 5 6,  Elke Mühlberger 5 6,  Emmett V Schmidt 7,  Gene G Olinger 2 5 6 8,  Lynda M Stuart 1 9,  Adam Lacy-Hulbert 10 11
Affiliations

Affiliations

  • 1 Benaroya Research Institute, Seattle, WA 98101, USA.
  • 2 National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility, Frederick, MD 21702, USA.
  • 3 Massachusetts General Hospital, Boston, MA 02114, USA.
  • 4 Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
  • 5 Boston University School of Medicine, Boston, MA 02118, USA.
  • 6 National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.
  • 7 Merck and Co., Inc, Kenilworth, NJ 07033, USA.
  • 8 MRIGlobal, Gaithersburg, MD 20878, USA.
  • 9 Bill and Melinda Gates Foundation, Seattle, WA 98109, USA.
  • 10 Benaroya Research Institute, Seattle, WA 98101, USA. [email protected].
  • 11 Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • # Contributed equally.
PMID: 32855215 DOI: 10.1126/science.abb3753
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.

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