Insect dome receptor directly recognizes viral envelopes to activate JAK/STAT signaling and induce conserved antiviral viperin expression

Summary: Insect Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays a crucial role in antiviral defense, yet how arboviruses activate this pathway remains unclear. Here, we reveal that outer capsid protein of a double-stranded RNA (dsRNA) arbovirus (rice gall dwarf...

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Bibliographic Details
Main Authors: Siyu Chen, Yupeng Tang, Chunyu Zhang, You Li, Dongsheng Jia, Taiyun Wei
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S221112472500926X
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Summary:Summary: Insect Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays a crucial role in antiviral defense, yet how arboviruses activate this pathway remains unclear. Here, we reveal that outer capsid protein of a double-stranded RNA (dsRNA) arbovirus (rice gall dwarf virus, RGDV) directly binds the Dome receptor’s extracellular domain, triggering receptor dimerization and JAK/STAT activation. Structural and mutational analyses pinpoint cysteine 743 in Dome as essential for viral recognition, establishing Dome as the first identified viral pattern recognition receptor (PRR) in insects capable of initiating JAK/STAT signaling, a pathway previously thought to be exclusively cytokine dependent. Furthermore, we identify viperin as a transcriptional factor STAT-regulated antiviral effector with broad-spectrum activity against multiple rice viruses. Intriguingly, RGDV’s nonstructural protein Pns11 competitively binds STAT, blocking its phosphorylation by JAK and nuclear translocation, thereby suppressing viperin expression. These findings elucidate how leafhopper Dome functions as a viral PRR and how arboviruses antagonize Dome-JAK-STAT signaling to promote persistent viral infection.
ISSN:2211-1247