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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Main Authors: Dongyi Zhao, Nao Morimoto, Riho Saito, Juri Yamada, Shuntaro Abe, Hidetaka Kosako, Yukiko Gotoh, Tomohiko Okazaki
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225015172
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Summary: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.
ISSN:2589-0042