A promiscuous inflammasome sparks replication of a common tumor virus.
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| Title: | A promiscuous inflammasome sparks replication of a common tumor virus. |
|---|---|
| Authors: | Burton, Eric M.1, Goldbach-Mansky, Raphaela2, Bhaduri-McIntosh, Sumita3,4 sbhadurimcintosh@ufl.edu |
| Source: | Proceedings of the National Academy of Sciences of the United States of America. 1/21/2020, Vol. 117 Issue 3, p1722-1730. 9p. |
| Subjects: | Oncogenic viruses, Post-translational modification, B cells, Epstein-Barr virus, Herpesviruses |
| Abstract: | Viruses activate inflammasomes but then subvert resulting inflammatory responses to avoid elimination. We asked whether viruses could instead use such activated or primed inflammasomes to directly aid their propagation and spread. Since herpesviruses are experts at coopting cellular functions, we investigated whether Epstein-Barr virus (EBV), an oncoherpesvirus, exploits inflammasomes to activate its replicative or lytic phase. Indeed, our experiments reveal that EBV exploits several inflammasome sensors to actually activate its replicative phase from quiescence/latency. In particular, TXNIP, a key inflammasome intermediary, causes assembly of the NLRP3 inflammasome, resulting in caspase-1-mediated depletion of the heterochromatin-inducing epigenetic repressor KAP1/TRIM28 in a subpopulation of cells. As a result, only TXNIPhiKAP1lo cells, that is, in a primed/prolytic state, turn expression of the replication/lytic/reactivation switch protein on to enter the replicative phase. Our findings 1) demonstrate that EBV dovetails its escape strategy to a key cellular danger-sensing mechanism, 2) indicate that transcription may be regulated by KAP1 abundance aside from canonical regulation through its posttranslational modification, 3) mechanistically link diabetes, which frequently activates the NLRP3 inflammasome, to deregulation of a tumor virus, and 4) demonstrate that B lymphocytes from NOMID (neonatal onset multisystem inflammatory disease) patients who have NLRP3 mutations and suffer from hyperactive innate responses are defective in controlling a herpesvirus. [ABSTRACT FROM AUTHOR] |
| Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 141360855 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: A promiscuous inflammasome sparks replication of a common tumor virus. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Burton%2C+Eric+M%2E%22">Burton, Eric M.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Goldbach-Mansky%2C+Raphaela%22">Goldbach-Mansky, Raphaela</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Bhaduri-McIntosh%2C+Sumita%22">Bhaduri-McIntosh, Sumita</searchLink><relatesTo>3,4</relatesTo><i> sbhadurimcintosh@ufl.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink>. 1/21/2020, Vol. 117 Issue 3, p1722-1730. 9p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Oncogenic+viruses%22">Oncogenic viruses</searchLink><br /><searchLink fieldCode="DE" term="%22Post-translational+modification%22">Post-translational modification</searchLink><br /><searchLink fieldCode="DE" term="%22B+cells%22">B cells</searchLink><br /><searchLink fieldCode="DE" term="%22Epstein-Barr+virus%22">Epstein-Barr virus</searchLink><br /><searchLink fieldCode="DE" term="%22Herpesviruses%22">Herpesviruses</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Viruses activate inflammasomes but then subvert resulting inflammatory responses to avoid elimination. We asked whether viruses could instead use such activated or primed inflammasomes to directly aid their propagation and spread. Since herpesviruses are experts at coopting cellular functions, we investigated whether Epstein-Barr virus (EBV), an oncoherpesvirus, exploits inflammasomes to activate its replicative or lytic phase. Indeed, our experiments reveal that EBV exploits several inflammasome sensors to actually activate its replicative phase from quiescence/latency. In particular, TXNIP, a key inflammasome intermediary, causes assembly of the NLRP3 inflammasome, resulting in caspase-1-mediated depletion of the heterochromatin-inducing epigenetic repressor KAP1/TRIM28 in a subpopulation of cells. As a result, only TXNIPhiKAP1lo cells, that is, in a primed/prolytic state, turn expression of the replication/lytic/reactivation switch protein on to enter the replicative phase. Our findings 1) demonstrate that EBV dovetails its escape strategy to a key cellular danger-sensing mechanism, 2) indicate that transcription may be regulated by KAP1 abundance aside from canonical regulation through its posttranslational modification, 3) mechanistically link diabetes, which frequently activates the NLRP3 inflammasome, to deregulation of a tumor virus, and 4) demonstrate that B lymphocytes from NOMID (neonatal onset multisystem inflammatory disease) patients who have NLRP3 mutations and suffer from hyperactive innate responses are defective in controlling a herpesvirus. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1073/pnas.1919133117 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 1722 Subjects: – SubjectFull: Oncogenic viruses Type: general – SubjectFull: Post-translational modification Type: general – SubjectFull: B cells Type: general – SubjectFull: Epstein-Barr virus Type: general – SubjectFull: Herpesviruses Type: general Titles: – TitleFull: A promiscuous inflammasome sparks replication of a common tumor virus. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Burton, Eric M. – PersonEntity: Name: NameFull: Goldbach-Mansky, Raphaela – PersonEntity: Name: NameFull: Bhaduri-McIntosh, Sumita IsPartOfRelationships: – BibEntity: Dates: – D: 21 M: 01 Text: 1/21/2020 Type: published Y: 2020 Identifiers: – Type: issn-print Value: 00278424 Numbering: – Type: volume Value: 117 – Type: issue Value: 3 Titles: – TitleFull: Proceedings of the National Academy of Sciences of the United States of America Type: main |
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