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

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Title: MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.
Authors: Bruchez, Anna, Sha, Ky, Johnson, Joshua, Chen, Li, Stefani, Caroline, McConnell, Hannah, Gaucherand, Lea, Prins, Rachel, Matreyek, Kenneth A., Hume, Adam J., Mühlberger, Elke, Schmidt, Emmett V., Olinger, Gene G., Stuart, Lynda M., Lacy-Hulbert, Adam
Source: Science (pre-March 2025). 10/9/2020, Vol. 370 Issue 6513, p241-247. 7p. 1 Diagram, 3 Graphs.
Subjects: Major histocompatibility complex, Ebola virus, SARS disease, Virus diseases, Antigen presentation
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 SARSCoV-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. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.
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  Data: <searchLink fieldCode="AR" term="%22Bruchez%2C+Anna%22">Bruchez, Anna</searchLink><br /><searchLink fieldCode="AR" term="%22Sha%2C+Ky%22">Sha, Ky</searchLink><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Joshua%22">Johnson, Joshua</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Li%22">Chen, Li</searchLink><br /><searchLink fieldCode="AR" term="%22Stefani%2C+Caroline%22">Stefani, Caroline</searchLink><br /><searchLink fieldCode="AR" term="%22McConnell%2C+Hannah%22">McConnell, Hannah</searchLink><br /><searchLink fieldCode="AR" term="%22Gaucherand%2C+Lea%22">Gaucherand, Lea</searchLink><br /><searchLink fieldCode="AR" term="%22Prins%2C+Rachel%22">Prins, Rachel</searchLink><br /><searchLink fieldCode="AR" term="%22Matreyek%2C+Kenneth+A%2E%22">Matreyek, Kenneth A.</searchLink><br /><searchLink fieldCode="AR" term="%22Hume%2C+Adam+J%2E%22">Hume, Adam J.</searchLink><br /><searchLink fieldCode="AR" term="%22Mühlberger%2C+Elke%22">Mühlberger, Elke</searchLink><br /><searchLink fieldCode="AR" term="%22Schmidt%2C+Emmett+V%2E%22">Schmidt, Emmett V.</searchLink><br /><searchLink fieldCode="AR" term="%22Olinger%2C+Gene+G%2E%22">Olinger, Gene G.</searchLink><br /><searchLink fieldCode="AR" term="%22Stuart%2C+Lynda+M%2E%22">Stuart, Lynda M.</searchLink><br /><searchLink fieldCode="AR" term="%22Lacy-Hulbert%2C+Adam%22">Lacy-Hulbert, Adam</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 10/9/2020, Vol. 370 Issue 6513, p241-247. 7p. 1 Diagram, 3 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Major+histocompatibility+complex%22">Major histocompatibility complex</searchLink><br /><searchLink fieldCode="DE" term="%22Ebola+virus%22">Ebola virus</searchLink><br /><searchLink fieldCode="DE" term="%22SARS+disease%22">SARS disease</searchLink><br /><searchLink fieldCode="DE" term="%22Virus+diseases%22">Virus diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Antigen+presentation%22">Antigen presentation</searchLink>
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  Label: Abstract
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  Data: 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 SARSCoV-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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1126/science.abb3753
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        Text: English
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      – SubjectFull: Major histocompatibility complex
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      – SubjectFull: Ebola virus
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      – SubjectFull: SARS disease
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      – SubjectFull: Virus diseases
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      – SubjectFull: Antigen presentation
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      – TitleFull: MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.
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              Text: 10/9/2020
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