MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.
Antigens, Differentiation, B-Lymphocyte
/ genetics
Betacoronavirus
/ physiology
COVID-19
Cell Line, Tumor
Coronavirus Infections
/ immunology
DNA Transposable Elements
Ebolavirus
/ physiology
Endosomes
/ virology
Genetic Testing
Hemorrhagic Fever, Ebola
/ immunology
Histocompatibility Antigens Class II
/ genetics
Host-Pathogen Interactions
/ genetics
Humans
Nuclear Proteins
/ genetics
Pandemics
Pneumonia, Viral
/ immunology
SARS-CoV-2
Trans-Activators
/ genetics
Transcription, Genetic
Virus Internalization
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
09 10 2020
09 10 2020
Historique:
received:
21
02
2020
accepted:
20
08
2020
pubmed:
29
8
2020
medline:
22
10
2020
entrez:
29
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32855215
pii: science.abb3753
doi: 10.1126/science.abb3753
pmc: PMC7665841
doi:
Substances chimiques
Antigens, Differentiation, B-Lymphocyte
0
DNA Transposable Elements
0
Histocompatibility Antigens Class II
0
MHC class II transactivator protein
0
Nuclear Proteins
0
Trans-Activators
0
invariant chain
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
241-247Subventions
Organisme : NIAID NIH HHS
ID : R21 AI135912
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI102266
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272200700016I
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI070330
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI119341
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U19 AI125378
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI036219
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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