Japanese Encephalitis Virus NS2B-3 Protein Complex Promotes Cell Apoptosis and Viral Particle Release by Down-Regulating the Expression of AXL

查看全文 作　　者：Shengda [1]Xie;Zhenjie [1]Liang;Xingmiao [1]Yang;Junhui [1]Pan;Du [1]Yu;Tongtong [1]Li;Ruibing [1]Cao

机构地区：[1]MOE Joint International Research Laboratory of Animal Health and Food Safety,College of Veterinary Medicine,Nanjing Agricultural University,Nanjing,210095,China

出　　处：《Virologica Sinica》索引2021年第36卷第6期,共17页

基　　金：This work was carried out with support of grants from the National Key Research and Development Plan of China(Grant No.2016YFD0500402);the National Natural Science Foundation of China(Grant No.31772756);the Priority Academic Program Development of Jiangsu Higher Education Institutions。 摘　　要：Japanese encephalitis virus(JEV) is a flavivirus transmitted by mosquitoes that causes severe encephalitis in humans and animals. It has been suggested that AXL, a transmembrane protein, can promote the replication of various flaviviruses,such as dengue(DENV), Zika(ZIKV), and West Nile(WNV) viruses. However, the effect of AXL on JEV infection has not yet been determined. In the present study, we demonstrate that AXL is down-regulated after JEV infection in the late stage. JEV NS2B-3 protein specifically interacted with AXL, and promoted AXL degradation through the ubiquitin–proteasome pathway. AXL-degradation increased cell apoptosis by disrupting phosphatidylinositol 3-kinase(PI3 K)/Akt signal transduction. In addition, the degradation of AXL promoted JEV release to supernatant, whereas the virus in the cell lysates decreased. The supplementation of AXL ligand Gas6 inhibited the JEV-mediated degradation of AXL. Altogether,we discover a new function of NS2B-3 during the process of JEV replication, and provide a new insight into the interactions between JEV and cell hosts. 关键词：Japanese encephalitis virus(JEV) AXL NS2B-3 Cell apoptosis Virus release

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Japanese Encephalitis Virus NS2B-3 Protein Complex Promotes Cell Apoptosis and Viral Particle Release by Down-Regulating the Expression of AXL

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