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Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation
The type I interferon (IFN) pathway is a key component of innate immune response upon invasion of foreign pathogens. It is also under precise control to prevent excessive upregulation and undesired inflammation cascade. In the present study, we report that Riok3, an atypical kinase, negatively regul...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363743/ https://www.ncbi.nlm.nih.gov/pubmed/34161773 http://dx.doi.org/10.1016/j.celrep.2021.109272 |
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author | Shen, Yong Tang, Kejun Chen, Dongdong Hong, Mengying Sun, Fangfang Wang, SaiSai Ke, Yuehai Wu, Tingting Sun, Ren Qian, Jing Du, Yushen |
author_facet | Shen, Yong Tang, Kejun Chen, Dongdong Hong, Mengying Sun, Fangfang Wang, SaiSai Ke, Yuehai Wu, Tingting Sun, Ren Qian, Jing Du, Yushen |
author_sort | Shen, Yong |
collection | PubMed |
description | The type I interferon (IFN) pathway is a key component of innate immune response upon invasion of foreign pathogens. It is also under precise control to prevent excessive upregulation and undesired inflammation cascade. In the present study, we report that Riok3, an atypical kinase, negatively regulates retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) sensing-induced type I IFN signaling. Riok3 deficiency selectively inhibits RNA viral replication in vitro, resulting from an upregulated type I IFN pathway. Mice with myeloid-specific Riok3 knockout also show a more robust induction of type I IFN upon RNA virus infection and are more resistant to RNA virus-induced pathogenesis. Mechanistically, Riok3 recruits and interacts with the E3 ubiquitin ligase TRIM40, leading to the degradation of RIG-I and melanoma differentiation-associated gene-5 (MDA5) via K48- and K27-linked ubiquitination. Collectively, our data reveal the mechanism that Riok3 employs to be a negative regulator of antiviral innate immunity. |
format | Online Article Text |
id | pubmed-8363743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-83637432021-08-14 Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation Shen, Yong Tang, Kejun Chen, Dongdong Hong, Mengying Sun, Fangfang Wang, SaiSai Ke, Yuehai Wu, Tingting Sun, Ren Qian, Jing Du, Yushen Cell Rep Article The type I interferon (IFN) pathway is a key component of innate immune response upon invasion of foreign pathogens. It is also under precise control to prevent excessive upregulation and undesired inflammation cascade. In the present study, we report that Riok3, an atypical kinase, negatively regulates retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) sensing-induced type I IFN signaling. Riok3 deficiency selectively inhibits RNA viral replication in vitro, resulting from an upregulated type I IFN pathway. Mice with myeloid-specific Riok3 knockout also show a more robust induction of type I IFN upon RNA virus infection and are more resistant to RNA virus-induced pathogenesis. Mechanistically, Riok3 recruits and interacts with the E3 ubiquitin ligase TRIM40, leading to the degradation of RIG-I and melanoma differentiation-associated gene-5 (MDA5) via K48- and K27-linked ubiquitination. Collectively, our data reveal the mechanism that Riok3 employs to be a negative regulator of antiviral innate immunity. 2021-06-22 /pmc/articles/PMC8363743/ /pubmed/34161773 http://dx.doi.org/10.1016/j.celrep.2021.109272 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Shen, Yong Tang, Kejun Chen, Dongdong Hong, Mengying Sun, Fangfang Wang, SaiSai Ke, Yuehai Wu, Tingting Sun, Ren Qian, Jing Du, Yushen Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation |
title | Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation |
title_full | Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation |
title_fullStr | Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation |
title_full_unstemmed | Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation |
title_short | Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation |
title_sort | riok3 inhibits the antiviral immune response by facilitating trim40-mediated rig-i and mda5 degradation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363743/ https://www.ncbi.nlm.nih.gov/pubmed/34161773 http://dx.doi.org/10.1016/j.celrep.2021.109272 |
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