Rhabdovirus Glycoprotein Triggers Janus Kinase/Signal Transducer and Activator of Transcription Antiviral Immunity via Direct Recognition by Insect Dome Receptor.

Abstract

Janus kinase/signal transducer and activator of transcription (JAK/STAT) immune response traditionally requires cytokine binding to receptors for activation; however, it remains unclear whether cytokine receptors function as direct pattern recognition receptors (PRRs) that recognise viral envelopes. In this study, we demonstrate that cytokine receptor Domeless (Dome) in leafhopper Recilia dorsalis directly recognises glycoprotein (G) of an important rice rhabdovirus. This binding induces Dome dimerisation, which initiates JAK/STAT pathway and leads to STAT-dependent expression of antiviral immune effector in R. dorsalis (RdIE1). RdIE1 suppresses viral replication by inhibiting the RNA-binding activity of viral large polymerase (L). Dome residue T659 is essential for G recognition and L residues E774 and D775 are required for RdIE1 target. Notably, virus-encoded phosphoprotein competitively inhibits the phosphorylation of STAT by casein kinase II (CK2β), thereby abrogating STAT-dependent transactivation of target genes. Our findings redefine Dome as a viral sensor and reveal a biphasic strategy that balances antiviral immunity with persistent viral infection in insect vectors.