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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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.
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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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