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 identify LmGypsy, a long terminal repeat (LTR) retrotransposon in Locusta migratoria, as a critical mediator of biphasic antiviral immunity against Acrididae reovirus (ARV). ARV infection triggers selective de-repression of LmGypsy, 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 insect cGAS homologs 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 highlight LmGypsy as a paradigm for understanding host-transposon coevolution in antiviral contexts.