Outbreaks of diseases are often linked to environmental stress,which can lead to endoplasmic reticulum(ER)stress and subsequently trigger the unfolded protein response(UPR).The replication of the white spot syndrome v...Outbreaks of diseases are often linked to environmental stress,which can lead to endoplasmic reticulum(ER)stress and subsequently trigger the unfolded protein response(UPR).The replication of the white spot syndrome virus(WSSV),the most serious pathogen in shrimp aquaculture,has been shown to rely on the UPR signaling pathway,although the detailed mechanisms remain poorly understood.In this study,we discovered that WSSV enhances its replication by hijacking the UPR pathway via the viral protein wsv406.Our analysis revealed a significant upregulation of wsv406 in the hemocytes and gills of infected shrimp.Mass spectrometry analysis identified that wsv406 interacts specifically with the immunoglobulin heavy-chain-binding protein(BiP)in shrimp Litopenaeus vannamei.Further examination revealed that wsv406 binds to multiple domains of LvBiP,inhibiting its ATPase activity without disrupting its binding to UPR stress receptors.Silencing either wsv406 or LvBiP resulted in a reduction in WSSV replication and improved shrimp survival rates.Further,wsv406 activation of the PRKR-like ER kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)and activating transcription factor 6(ATF6)pathways was demonstrated by a decrease in the phosphorylation of eIF2αand the nuclear translocation of ATF6 when wsv406 was silenced during WSSV infection.This activation facilitated the transcription of WSSV genes,promoting viral replication.In summary,these findings reveal that wsv406 manipulates the host UPR by targeting LvBiP,thereby enhancing WSSV replication through the PERK-eIF2αand ATF6 pathways.These insights into the interaction between WSSV and host cellular machinery offer potential targets for developing therapeutic interventions to control WSSV outbreaks in shrimp aquaculture.展开更多
基金supported by the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(SML2023SP234)National Natural Science Foundation of China(32022085/32373158/31930113)the open competition program of top ten critical priorities of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province(2022SDZG01).
文摘Outbreaks of diseases are often linked to environmental stress,which can lead to endoplasmic reticulum(ER)stress and subsequently trigger the unfolded protein response(UPR).The replication of the white spot syndrome virus(WSSV),the most serious pathogen in shrimp aquaculture,has been shown to rely on the UPR signaling pathway,although the detailed mechanisms remain poorly understood.In this study,we discovered that WSSV enhances its replication by hijacking the UPR pathway via the viral protein wsv406.Our analysis revealed a significant upregulation of wsv406 in the hemocytes and gills of infected shrimp.Mass spectrometry analysis identified that wsv406 interacts specifically with the immunoglobulin heavy-chain-binding protein(BiP)in shrimp Litopenaeus vannamei.Further examination revealed that wsv406 binds to multiple domains of LvBiP,inhibiting its ATPase activity without disrupting its binding to UPR stress receptors.Silencing either wsv406 or LvBiP resulted in a reduction in WSSV replication and improved shrimp survival rates.Further,wsv406 activation of the PRKR-like ER kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)and activating transcription factor 6(ATF6)pathways was demonstrated by a decrease in the phosphorylation of eIF2αand the nuclear translocation of ATF6 when wsv406 was silenced during WSSV infection.This activation facilitated the transcription of WSSV genes,promoting viral replication.In summary,these findings reveal that wsv406 manipulates the host UPR by targeting LvBiP,thereby enhancing WSSV replication through the PERK-eIF2αand ATF6 pathways.These insights into the interaction between WSSV and host cellular machinery offer potential targets for developing therapeutic interventions to control WSSV outbreaks in shrimp aquaculture.
