Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways

作者全名："Zhao, Zhenyu; Wei, Zhen; Zheng, Jiaxin; Li, Zhihong; Zou, Hecun; Wen, Xiang; Li, Fahong; Wang, Xueyu; Huang, Qian; Zeng, Huaqing; Fan, Hui; Cai, Xuefei; Zhang, Jiming; Jia, Bei; Huang, Ailong; Lu, Mengji; Lin, Yong"

作者地址："[Zhao, Zhenyu; Wei, Zhen; Zheng, Jiaxin; Li, Zhihong; Huang, Qian; Zeng, Huaqing; Fan, Hui; Cai, Xuefei; Huang, Ailong; Lin, Yong] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Chinese Minist Educ, Chongqing, Peoples R China; [Zou, Hecun] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Wen, Xiang; Jia, Bei] Chongqing Med Univ, Dept Infect Dis, Key Lab Infect & Parasit Dis Chongqing, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Fahong; Zhang, Jiming] Fudan Univ, Huashan Hosp, Dept Infect Dis, Shanghai, Peoples R China; [Wang, Xueyu; Lu, Mengji] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany; [Lin, Yong] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Chinese Minist Educ, Chongqing 400016, Peoples R China"

通信作者："Lin, Y (通讯作者)，Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Chinese Minist Educ, Chongqing 400016, Peoples R China."

来源：EMERGING MICROBES & INFECTIONS

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001088857500001

JCR分区：Q1

影响因子：8.4

年份：2023

卷号：12

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Hepatitis B virus; RAB5A; autophagy; endosome; VPS34

摘要："Chronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been well elucidated how HBV exploits such intracellular vesicle systems for its replication. RAB5A, a member of small GTPase family, plays crucial roles in early endosome biogenesis and autophagy initiation. We observed that RAB5A mRNA and protein levels were significantly increased in HBV-expressing hepatoma cell lines as well as in liver tissue samples from chronic HBV-infected patients. Moreover, RAB5A silencing inhibited HBV replication and subviral particle (SVP) expression significantly in HBV-transfected and -infected hepatoma cells, whereas RAB5A overexpression increased them. Mechanistically, RAB5A increases HBV replication through enhancement of early endosome (EE) - late endosome (LE) activation by interacting with EEA1, as well as enhancing autophagy induction by interacting with VPS34. Additionally, HBV infection enhances RAB5A-mediated dual activation of EE-LE system and autophagy. Collectively, our findings highlight that HBV utilizes RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways for its own replication and persistence. Therefore, RAB5A is a potential target for chronic HBV infection treatment."

基金机构："National Key Research and Development Program of China [2022YFA1303600]; National Natural Science Foundation of China [82002131]; Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission [cstc2020jcyj-msxmX0081]; Key Scientific and Technological Innovation Project from Chongqing Municipal Education Commission [KJCXZD2020018]; Program for Youth Innovation in Future Medicine from Chongqing Medical University [W0066]; Deutsche Forschungsgemeinschaft [RTG1949/2]"

基金资助正文："This work was supported by grants from the National Key Research and Development Program of China [grant number 2022YFA1303600], National Natural Science Foundation of China [grant number 82002131], Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission [grant number cstc2020jcyj-msxmX0081], Key Scientific and Technological Innovation Project from Chongqing Municipal Education Commission [grant number KJCXZD2020018], Program for Youth Innovation in Future Medicine from Chongqing Medical University [grant number W0066], and Deutsche Forschungsgemeinschaft [grant number RTG1949/2]."