Locust cGAS-like receptors recognize derivatives of a Gypsy retrotransposon to synergize with RNAi against viral invasion

The co-option of transposable elements (TEs) as immune sentinels represents an evolutionarily conserved strategy across metazoans, yet the molecular mechanisms linking retrotransposon reactivation to antiviral defense remain enigmatic. Here, we identifyLmGypsy, a long terminal repeat (LTR) retrotransposon inLocusta migratoria, as a critical mediator of biphasic antiviral immunity againstAcrididae reovirus(ARV). ARV infection triggers selective de-repression ofLmGypsy, which orchestrates dual antiviral pathways: (1) its encoded reverse transcriptase synthesizes viral DNA (vDNA) from ARV RNA, fueling RNA interference (RNAi)-mediated viral RNA degradation through Dicer-2-dependent vsiRNA biogenesis; (2) LmGypsy-derived nucleic acids activate cGAS-like receptors (LmcGASs) and induce immune responses. Strikingly, vDNA persists in infected locusts from 24 h post-infection until host death, suggesting a role in sustaining antiviral activity akin to immune memory mechanisms observed in Diptera. This study provides the first evidence that insectcGAShomologs function as retrotransposon sensors, mirroring mammalian cGAS-STING recognition of endogenous retroviral elements. Our findings redefine retrotransposons as central hubs in arthropod antiviral immunity, bridging RNAi and nucleic acid-sensing pathways to establish a coordinated defense network. These results illuminate conserved principles of TE-immune crosstalk and highlightLmGypsyas a paradigm for understanding host-transposon coevolution in antiviral contexts.