Bracovirus sneaks into apoptotic bodies transmitting immunosuppressive signaling driven by integration-mediated eIF5A hypusination

The typical characteristic of polydnavirus (PDV) infection is persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, how Microplitis bicoloratus bracovirus (MbBV) activates caspase-3 to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, little is known about how inserted viral fragments interact with host cells to drive apoptosis and the role MbBV-mediated extracellular vesicles play in immune suppression. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cell apoptosis and dismigration. Overall, viral host integrated motif sites insertion damaged host genome stimulating eIF5A nucleocytoplasmic transport, activating the eIF5A-hypusination translation pathway. Functionally, translated apoptosis-related host proteins, such as P53, CypD, CypJ, and CypA, drive a broken dsDNA cellular apoptosis. Furthermore, translated viral proteins, vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination translation pathway. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 level via pI3K/Akt 308 and 473 dephosphorylation to promote recipients cell apoptosis; pI3K/Akt 473 phosphorylation inhibited caspase-3 activation leading to recipient cell dismigration. In conclusion, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continues immunosuppressive.