Modulation of the unfolded protein response by white spot syndrome virus via wsv406 targeting BiP to facilitate viral replication  

作　　者：Shihan Chen Qiqi Zhong Xuzheng Liao Haiyang Wang Bang Xiao Jianguo He Chaozheng Li 

机构地区：[1]School of Marine Sciences,Sun Yat-sen University,State Key Laboratory of Biocontrol/Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai),Guangzhou,510275,China [2]Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering/Guangdong Provincial Key Laboratory for Aquatic Economic Animals,Sun Yat-sen University,Guangzhou,510275,China [3]China-ASEAN Belt and Road Joint Laboratory on Marine Aquaculture Technology,Sun Yat-sen University,Guangzhou,510275,China

出　　处：《Virologica Sinica》2024年第6期938-950,共13页中国病毒学(英文版)

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).

摘　　要：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.

关 键 词：SHRIMP White spot syndrome virus Unfolded protein response wsv406 Binding protein(BiP) 

分 类 号：R373[医药卫生—病原生物学]