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

## TL;DR

This study shows how a plant virus activates antiviral defenses in insect vectors by triggering ER-phagy through a stress response pathway.

## Contribution

The study reveals a novel antiviral mechanism in insects where a viral glycoprotein activates ER-phagy via the UPR pathway.

## Key findings

- RSMV glycoprotein disrupts BiP-PERK interaction to activate the UPR pathway.
- ATF4 regulates ATG8 expression, linking UPR to autophagy and ER-phagy.
- ER-phagy receptors like Sec62 are recruited to degrade viral particles and ER fragments.

## Abstract

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.

This study investigate how rice stripe mosaic virus (RSMV) manipulates its insect vectors to induce ER-phagy. We discover that the viral glycoprotein G disrupts the normal function of the ER chaperone BiP, which in turn activates the PERK-ATF4 stress signaling pathway. Subsequently, this pathway triggers the expression of autophagy-related gene and recruits the ER-phagy receptor Sec62, leading to the formation of autophagosomes that capture and degrade both viral particles and damaged ER components. These results demonstrate that the viral envelope protein is sensed by insect vectors to induce antiviral ER-phagy, thereby uncovering a previously unknown antiviral strategy in insects.