Release of hepatitis B virions is positively regulated by glucose-regulated protein 78 through direct interaction with preS1

作者全名："Shi, Yueyuan; Jin, Xin; Wu, Shuang; Liu, Junye; Zhang, Hongpeng; Cai, Xuefei; Yang, Yuan; Zhang, Xiang; Wei, Jie; Luo, Miao; Zhou, Hua; Zhou, Huihao; Huang, Ailong; Wang, Deqiang"

作者地址："[Shi, Yueyuan; Wu, Shuang; Liu, Junye; Zhang, Hongpeng; Cai, Xuefei; Yang, Yuan; Huang, Ailong; Wang, Deqiang] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Chinese Minist Educ, Chongqing 400016, Peoples R China; [Shi, Yueyuan; Jin, Xin; Zhang, Xiang; Wei, Jie; Wang, Deqiang] Chongqing Med Univ, Coll Lab Med, Chongqing, Peoples R China; [Shi, Yueyuan; Luo, Miao] Peoples Hosp Yubei Dist Chongqing City, Dept Clin Lab, Chongqing, Peoples R China; [Jin, Xin] Second Hosp Harbin, Dept Clin Lab, Harbin, Heilongjiang, Peoples R China; [Wu, Shuang] Affiliated Children Hosp Xian Jiaotong Univ, Dept Clin Lab, Xian, Shanxi, Peoples R China; [Liu, Junye] Xi An Jiao Tong Univ, Honghui Hosp, Dept Clin Lab, Xian, Shanxi, Peoples R China; [Zhang, Hongpeng] Women & Childrens Hosp Chongqing Med Univ, Dept Blood Transfus, Chongqing, Peoples R China; [Zhou, Hua] Chongqing Med Univ, Dept Clin Lab, Affiliated Hosp 2, Chongqing, Peoples R China; [Zhou, Huihao] Sun Yat Sen Univ, Sch Pharmaceut Sci, Res Ctr Drug Discovery, Guangzhou, Peoples R China"

通信作者："Huang, AL; Wang, DQ (通讯作者)，Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Chinese Minist Educ, Chongqing 400016, Peoples R China."

来源：JOURNAL OF MEDICAL VIROLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000911465200191

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：95

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：antiviral; enveloped particles; GRP78; hepatitis B virus; peptide; virion release

摘要："In this study, we investigated the mechanism of hepatitis B virus (HBV)-enveloped particle release. Specifically, we used preS1 as a bait protein to screen host proteins using mass spectroscopy, with the results of immunofluorescence, western blot, co-immunoprecipitation, isothermal titration calorimetry, and pull-down assays identifying glucose-regulated protein (GRP)78 as a specific target for preS1 binding. We employed transcriptome sequencing, enzyme-linked immunosorbent assays, and particle gel assays to investigate the mechanism of GRP78-mediated positive regulation of HBV-enveloped particle release. Additionally, we performed phage-display, surface plasmon resonance, and molecular-docking assays to assess peptides inhibiting enveloped-particle release. We found that HBV upregulated GRP78 expression in liver cell lines and the serum of patients with chronic hepatitis B. Furthermore, GRP78 promoted the release of HBV-enveloped particles in vitro and in vivo within an HBV transgenic mouse model. Moreover, we identified interactions of preS1 peptides with GRP78 via hydrogen bonding and hydrophobic interactions, which effectively inhibited its interaction with HBV-enveloped particles and their subsequent release. These findings provide novel insights regarding HBV virion release, and demonstrated that GRP78 interacted with preS1 to positively regulate the release of HBV-enveloped particles, suggesting GRP78 as a potential therapeutic target for inhibiting HBV infection."

基金机构：National Science and Technology Major Project; Municipal Natural Science Foundation of Chongqing; National Natural Science Foundation of China; CQMU Program for Youth Innovation in Future Medicine [W0031]; Chongqing Talents Program

基金资助正文：National Science and Technology Major Project; Municipal Natural Science Foundation of Chongqing; National Natural Science Foundation of China; CQMU Program for Youth Innovation in Future Medicine (W0031); Chongqing Talents Program