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MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.
Science. 2020 10 09; 370(6513):241-247.Sci

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.

Authors+Show Affiliations

Benaroya Research Institute, Seattle, WA 98101, USA.Benaroya Research Institute, Seattle, WA 98101, USA.National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility, Frederick, MD 21702, USA.Massachusetts General Hospital, Boston, MA 02114, USA.Benaroya Research Institute, Seattle, WA 98101, USA.Benaroya Research Institute, Seattle, WA 98101, USA.Benaroya Research Institute, Seattle, WA 98101, USA.Benaroya Research Institute, Seattle, WA 98101, USA.Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.Boston University School of Medicine, Boston, MA 02118, USA. National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.Boston University School of Medicine, Boston, MA 02118, USA. National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.Merck and Co., Inc, Kenilworth, NJ 07033, USA.National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility, Frederick, MD 21702, USA. Boston University School of Medicine, Boston, MA 02118, USA. National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA. MRIGlobal, Gaithersburg, MD 20878, USA.Benaroya Research Institute, Seattle, WA 98101, USA. Bill and Melinda Gates Foundation, Seattle, WA 98109, USA.Benaroya Research Institute, Seattle, WA 98101, USA. alacyhulbert@benaroyaresearch.org. Department of Immunology, University of Washington, Seattle, WA 98109, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32855215

Citation

Bruchez, Anna, et al. "MHC Class II Transactivator CIITA Induces Cell Resistance to Ebola Virus and SARS-like Coronaviruses." Science (New York, N.Y.), vol. 370, no. 6513, 2020, pp. 241-247.
Bruchez A, Sha K, Johnson J, et al. MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses. Science. 2020;370(6513):241-247.
Bruchez, A., Sha, K., Johnson, J., Chen, L., Stefani, C., McConnell, H., Gaucherand, L., Prins, R., Matreyek, K. A., Hume, A. J., Mühlberger, E., Schmidt, E. V., Olinger, G. G., Stuart, L. M., & Lacy-Hulbert, A. (2020). MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses. Science (New York, N.Y.), 370(6513), 241-247. https://doi.org/10.1126/science.abb3753
Bruchez A, et al. MHC Class II Transactivator CIITA Induces Cell Resistance to Ebola Virus and SARS-like Coronaviruses. Science. 2020 10 9;370(6513):241-247. PubMed PMID: 32855215.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses. AU - Bruchez,Anna, AU - Sha,Ky, AU - Johnson,Joshua, AU - Chen,Li, AU - Stefani,Caroline, AU - McConnell,Hannah, AU - Gaucherand,Lea, AU - Prins,Rachel, AU - Matreyek,Kenneth A, AU - Hume,Adam J, AU - Mühlberger,Elke, AU - Schmidt,Emmett V, AU - Olinger,Gene G, AU - Stuart,Lynda M, AU - Lacy-Hulbert,Adam, Y1 - 2020/08/27/ PY - 2020/02/21/received PY - 2020/08/20/accepted PY - 2020/8/29/pubmed PY - 2020/10/22/medline PY - 2020/8/29/entrez SP - 241 EP - 247 JF - Science (New York, N.Y.) JO - Science VL - 370 IS - 6513 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32855215/MHC_class_II_transactivator_CIITA_induces_cell_resistance_to_Ebola_virus_and_SARS_like_coronaviruses_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=32855215 DB - PRIME DP - Unbound Medicine ER -