A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases
Upon infection, viral nucleic acids are recognized by germline-encoded pattern-recognition receptors (PRRs), and cytosolic retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) that initiate signaling pathways resulting in the production of type I IFN and pro-inflammatory cytokines. Binding o...
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2018-04-01
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| Series: | Microbial Cell |
| Subjects: | |
| Online Access: | http://microbialcell.com/researcharticles/a-novel-mechanism-for-regulation-of-the-type-i-ifn-response-by-herpesvirus-deconjugases/ |
| _version_ | 1818257595886993408 |
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| author | Soham Gupta Päivi Ylä-Anttila Maria G. Masucci |
| author_facet | Soham Gupta Päivi Ylä-Anttila Maria G. Masucci |
| author_sort | Soham Gupta |
| collection | DOAJ |
| description | Upon infection, viral nucleic acids are recognized by germline-encoded pattern-recognition receptors (PRRs), and cytosolic retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) that initiate signaling pathways resulting in the production of type I IFN and pro-inflammatory cytokines. Binding of RIG-I to viral nucleic acids triggers the formation of the RIG-I signalosome where RIG-I is ubiquitinated by the TRIM25 ligase and, with the help of 14-3-3 scaffolds, further translocated to mitochondrial anti-viral signalling proteins (MAVS). Subsequent ubiquitination-mediated events trigger transcriptional activation of the effectors of innate immunity. We have found a new mechanism by which herpesviruses interfere with this signalling pathway to favour the establishment of latency and promote virus replication. The cysteine protease encoded in the conserved N-terminal domain of the herpesvirus large tegument protein binds to 14-3-3 proteins and forms a tri-molecular complex with TRIM25, promoting the activation and autoubiquitination of the ligase. RIG-I is recruited to the complex but its ubiquitination is drastically reduced, which effectively inactivates downstream signalling and blocks the type I IFN response. |
| first_indexed | 2024-12-12T17:46:09Z |
| format | Article |
| id | doaj.art-fc320c6dca1c4b2fa5ede97548092ff8 |
| institution | Directory Open Access Journal |
| issn | 2311-2638 |
| language | English |
| last_indexed | 2024-12-12T17:46:09Z |
| publishDate | 2018-04-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj.art-fc320c6dca1c4b2fa5ede97548092ff82022-12-22T00:16:56ZengShared Science Publishers OGMicrobial Cell2311-26382018-04-015525926110.15698/mic2018.05.633A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugasesSoham Gupta0Päivi Ylä-Anttila1Maria G. Masucci2Department of Cell and Molecular Biology, Karolinska Institutet, S-17177 Stockholm, Sweden.Department of Cell and Molecular Biology, Karolinska Institutet, S-17177 Stockholm, Sweden.Department of Cell and Molecular Biology, Karolinska Institutet, S-17177 Stockholm, Sweden.Upon infection, viral nucleic acids are recognized by germline-encoded pattern-recognition receptors (PRRs), and cytosolic retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) that initiate signaling pathways resulting in the production of type I IFN and pro-inflammatory cytokines. Binding of RIG-I to viral nucleic acids triggers the formation of the RIG-I signalosome where RIG-I is ubiquitinated by the TRIM25 ligase and, with the help of 14-3-3 scaffolds, further translocated to mitochondrial anti-viral signalling proteins (MAVS). Subsequent ubiquitination-mediated events trigger transcriptional activation of the effectors of innate immunity. We have found a new mechanism by which herpesviruses interfere with this signalling pathway to favour the establishment of latency and promote virus replication. The cysteine protease encoded in the conserved N-terminal domain of the herpesvirus large tegument protein binds to 14-3-3 proteins and forms a tri-molecular complex with TRIM25, promoting the activation and autoubiquitination of the ligase. RIG-I is recruited to the complex but its ubiquitination is drastically reduced, which effectively inactivates downstream signalling and blocks the type I IFN response.http://microbialcell.com/researcharticles/a-novel-mechanism-for-regulation-of-the-type-i-ifn-response-by-herpesvirus-deconjugases/Epstein-Barr virusHerpesvirusdeconjugaseRIG-I signalosometype I IFN |
| spellingShingle | Soham Gupta Päivi Ylä-Anttila Maria G. Masucci A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases Microbial Cell Epstein-Barr virus Herpesvirus deconjugase RIG-I signalosome type I IFN |
| title | A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases |
| title_full | A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases |
| title_fullStr | A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases |
| title_full_unstemmed | A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases |
| title_short | A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases |
| title_sort | novel mechanism for regulation of the type i ifn response by herpesvirus deconjugases |
| topic | Epstein-Barr virus Herpesvirus deconjugase RIG-I signalosome type I IFN |
| url | http://microbialcell.com/researcharticles/a-novel-mechanism-for-regulation-of-the-type-i-ifn-response-by-herpesvirus-deconjugases/ |
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