MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunity
Summary: Upon viral infection, cytosolic RIG-I-like receptors recognize viral RNA and activate innate immune responses through the mitochondrial antiviral-signaling protein (MAVS), leading to type I interferon (IFN) production and apoptosis. Cellular stress influences immune activation, but its impa...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225015172 |
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| author | Dongyi Zhao Nao Morimoto Riho Saito Juri Yamada Shuntaro Abe Hidetaka Kosako Yukiko Gotoh Tomohiko Okazaki |
| author_facet | Dongyi Zhao Nao Morimoto Riho Saito Juri Yamada Shuntaro Abe Hidetaka Kosako Yukiko Gotoh Tomohiko Okazaki |
| author_sort | Dongyi Zhao |
| collection | DOAJ |
| description | Summary: Upon viral infection, cytosolic RIG-I-like receptors recognize viral RNA and activate innate immune responses through the mitochondrial antiviral-signaling protein (MAVS), leading to type I interferon (IFN) production and apoptosis. Cellular stress influences immune activation, but its impact on MAVS signaling remains largely unclear. Here, we show that MAVS undergoes phosphorylation via p38 MAPK signaling, activated by the stress-activated MAPKKK ASK1. This modification enhances MAVS interaction with TRAF, a key downstream adaptor, thereby promoting type I IFN induction. Oxidative and endoplasmic reticulum stress significantly amplified type I IFN expression upon viral infection, but this effect was attenuated in cells expressing MAVS mutants lacking phosphorylation sites. These findings suggest MAVS phosphorylation as a key mechanism integrating cellular stress signals into antiviral immunity. By linking the MAPK pathway to MAVS-dependent IFN expression, we propose MAVS phosphorylation as a cellular stress sensor that modulates antiviral immunity in a context-dependent manner. |
| format | Article |
| id | doaj-art-be57ad9ff5b64a8a8aadbc4ce4b06fa0 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-be57ad9ff5b64a8a8aadbc4ce4b06fa02025-08-20T04:01:03ZengElsevieriScience2589-00422025-09-0128911325610.1016/j.isci.2025.113256MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunityDongyi Zhao0Nao Morimoto1Riho Saito2Juri Yamada3Shuntaro Abe4Hidetaka Kosako5Yukiko Gotoh6Tomohiko Okazaki7Laboratory of Molecular Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, JapanLaboratory of Molecular Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, JapanLaboratory of Molecular Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, JapanLaboratory of Molecular Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, JapanLaboratory of Molecular Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, JapanInstitute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, JapanGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo 113-0033, JapanLaboratory of Molecular Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan; Japan Science and Technology Agency (JST) Fusion Oriented Research for Disruptive Science and Technology (FOREST) Program, Kawaguchi 332-0012, Japan; Corresponding authorSummary: Upon viral infection, cytosolic RIG-I-like receptors recognize viral RNA and activate innate immune responses through the mitochondrial antiviral-signaling protein (MAVS), leading to type I interferon (IFN) production and apoptosis. Cellular stress influences immune activation, but its impact on MAVS signaling remains largely unclear. Here, we show that MAVS undergoes phosphorylation via p38 MAPK signaling, activated by the stress-activated MAPKKK ASK1. This modification enhances MAVS interaction with TRAF, a key downstream adaptor, thereby promoting type I IFN induction. Oxidative and endoplasmic reticulum stress significantly amplified type I IFN expression upon viral infection, but this effect was attenuated in cells expressing MAVS mutants lacking phosphorylation sites. These findings suggest MAVS phosphorylation as a key mechanism integrating cellular stress signals into antiviral immunity. By linking the MAPK pathway to MAVS-dependent IFN expression, we propose MAVS phosphorylation as a cellular stress sensor that modulates antiviral immunity in a context-dependent manner.http://www.sciencedirect.com/science/article/pii/S2589004225015172BiochemistryImmune responseCell biology |
| spellingShingle | Dongyi Zhao Nao Morimoto Riho Saito Juri Yamada Shuntaro Abe Hidetaka Kosako Yukiko Gotoh Tomohiko Okazaki MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunity iScience Biochemistry Immune response Cell biology |
| title | MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunity |
| title_full | MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunity |
| title_fullStr | MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunity |
| title_full_unstemmed | MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunity |
| title_short | MAVS phosphorylation acts as a cellular stress sensor that modulates antiviral immunity |
| title_sort | mavs phosphorylation acts as a cellular stress sensor that modulates antiviral immunity |
| topic | Biochemistry Immune response Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225015172 |
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