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WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response
RIG-I-MAVS signaling pathway plays a crucial role in defending against pathogen infection and maintaining immune balance. Upon detecting viral RNA, RIG-I triggers the formation of prion-like aggregates of the adaptor protein MAVS, which then activates the innate antiviral immune response. However, t...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415273/ https://www.ncbi.nlm.nih.gov/pubmed/37563140 http://dx.doi.org/10.1038/s41467-023-40567-5 |
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author | Li, Jiaxin Zhang, Rui Wang, Changwan Zhu, Junyan Ren, Miao Jiang, Yingbo Hou, Xianteng Du, Yangting Wu, Qing Qi, Shishi Li, Lin Chen, She Yang, Hui Hou, Fajian |
author_facet | Li, Jiaxin Zhang, Rui Wang, Changwan Zhu, Junyan Ren, Miao Jiang, Yingbo Hou, Xianteng Du, Yangting Wu, Qing Qi, Shishi Li, Lin Chen, She Yang, Hui Hou, Fajian |
author_sort | Li, Jiaxin |
collection | PubMed |
description | RIG-I-MAVS signaling pathway plays a crucial role in defending against pathogen infection and maintaining immune balance. Upon detecting viral RNA, RIG-I triggers the formation of prion-like aggregates of the adaptor protein MAVS, which then activates the innate antiviral immune response. However, the mechanisms that regulate the aggregation of MAVS are not yet fully understood. Here, we identified WDR77 as a MAVS-associated protein, which negatively regulates MAVS aggregation. WDR77 binds to MAVS proline-rich region through its WD2-WD3-WD4 domain and inhibits the formation of prion-like filament of recombinant MAVS in vitro. In response to virus infection, WDR77 is recruited to MAVS to prevent the formation of its prion-like aggregates and thus downregulate RIG-I-MAVS signaling in cells. WDR77 deficiency significantly potentiates the induction of antiviral genes upon negative-strand RNA virus infections, and myeloid-specific Wdr77-deficient mice are more resistant to RNA virus infection. Our findings reveal that WDR77 acts as a negative regulator of the RIG-I-MAVS signaling pathway by inhibiting the prion-like aggregation of MAVS to prevent harmful inflammation. |
format | Online Article Text |
id | pubmed-10415273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104152732023-08-12 WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response Li, Jiaxin Zhang, Rui Wang, Changwan Zhu, Junyan Ren, Miao Jiang, Yingbo Hou, Xianteng Du, Yangting Wu, Qing Qi, Shishi Li, Lin Chen, She Yang, Hui Hou, Fajian Nat Commun Article RIG-I-MAVS signaling pathway plays a crucial role in defending against pathogen infection and maintaining immune balance. Upon detecting viral RNA, RIG-I triggers the formation of prion-like aggregates of the adaptor protein MAVS, which then activates the innate antiviral immune response. However, the mechanisms that regulate the aggregation of MAVS are not yet fully understood. Here, we identified WDR77 as a MAVS-associated protein, which negatively regulates MAVS aggregation. WDR77 binds to MAVS proline-rich region through its WD2-WD3-WD4 domain and inhibits the formation of prion-like filament of recombinant MAVS in vitro. In response to virus infection, WDR77 is recruited to MAVS to prevent the formation of its prion-like aggregates and thus downregulate RIG-I-MAVS signaling in cells. WDR77 deficiency significantly potentiates the induction of antiviral genes upon negative-strand RNA virus infections, and myeloid-specific Wdr77-deficient mice are more resistant to RNA virus infection. Our findings reveal that WDR77 acts as a negative regulator of the RIG-I-MAVS signaling pathway by inhibiting the prion-like aggregation of MAVS to prevent harmful inflammation. Nature Publishing Group UK 2023-08-10 /pmc/articles/PMC10415273/ /pubmed/37563140 http://dx.doi.org/10.1038/s41467-023-40567-5 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Li, Jiaxin Zhang, Rui Wang, Changwan Zhu, Junyan Ren, Miao Jiang, Yingbo Hou, Xianteng Du, Yangting Wu, Qing Qi, Shishi Li, Lin Chen, She Yang, Hui Hou, Fajian WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response |
title | WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response |
title_full | WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response |
title_fullStr | WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response |
title_full_unstemmed | WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response |
title_short | WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response |
title_sort | wdr77 inhibits prion-like aggregation of mavs to limit antiviral innate immune response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415273/ https://www.ncbi.nlm.nih.gov/pubmed/37563140 http://dx.doi.org/10.1038/s41467-023-40567-5 |
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