Plant rhabdovirus glycoprotein activates unfolded protein response-mediated antiviral ER-phagy in insect vectors.

Although viral infection-induced endoplasmic reticulum autophagy (ER-phagy) is well characterized in mammalian systems, the mechanisms underlying arbovirus-triggered ER-phagy in insect vectors remain poorly understood. This study demonstrates that rice stripe mosaic virus (RSMV), a cytorhabdovirus transmitted by leafhopper vectors, activates the unfolded protein response (UPR) to induce ER-phagy as an antiviral defense mechanism. During viral assembly in the ER lumen, RSMV glycoprotein (G) disrupts the interaction between ER chaperone BiP and ER kinase PERK, leading to the release of PERK to activate subsequent signaling cascade. This ultimately activates the transcription factor ATF4, which regulates the expression of the autophagy-related gene ATG8, thereby linking the UPR to autophagy. Mechanistically, RSMV assembly promotes the formation of ER-derived amorphous inclusions that recruit ATG8 through interaction with ER-phagy receptor Sec62. This process culminates in the sequestration of both viral particles and ER fragments into autophagosomes, initiating ER-phagy triggered by viral infection. Functional studies confirmed that microinjection of RSMV G activates both the UPR and ER-phagy, while knockdown of PERK, ATF4, ATG8, or Sec62 significantly enhances viral accumulation, underscoring their essential antiviral roles. Our findings reveal a conserved nature of UPR-induced ER-phagy across vertebrate and invertebrate systems, advancing our understanding of arbovirus-vector interactions and antiviral defense mechanisms.