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.
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / physiology*
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Betacoronavirus / physiology*
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COVID-19
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Cell Line, Tumor
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Coronavirus Infections / immunology*
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Coronavirus Infections / virology
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DNA Transposable Elements
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Ebolavirus / physiology*
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Endosomes / virology
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Genetic Testing
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Hemorrhagic Fever, Ebola / immunology*
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Hemorrhagic Fever, Ebola / virology
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / physiology*
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Host-Pathogen Interactions / genetics
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Host-Pathogen Interactions / immunology*
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Humans
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Pandemics
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Pneumonia, Viral / immunology*
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Pneumonia, Viral / virology
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SARS-CoV-2
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Trans-Activators / genetics
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Trans-Activators / physiology*
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Transcription, Genetic
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Virus Internalization*
Substances
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Antigens, Differentiation, B-Lymphocyte
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DNA Transposable Elements
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Histocompatibility Antigens Class II
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MHC class II transactivator protein
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Nuclear Proteins
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Trans-Activators
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invariant chain