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CCDC88A/GIV 通过增强内体运输和阻断自噬降解促进 HBV 复制和子代分泌。

CCDC88A/GIV promotes HBV replication and progeny secretion via enhancing endosomal trafficking and blocking autophagic degradation.

机构信息

Institute of Biomedical Research, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei province, China.

Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

出版信息

Autophagy. 2022 Feb;18(2):357-374. doi: 10.1080/15548627.2021.1934271. Epub 2021 Jun 30.

DOI:10.1080/15548627.2021.1934271
PMID:34190023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8942511/
Abstract

Hepatitis B virus (HBV) particles are thought to be secreted from hepatocytes through multivesicular bodies (MVBs); however, the cellular trafficking mechanisms prior to this process remain elusive. It has been reported that CCDC88A/GIV expression, which is involved in multiple aspects of vesicular trafficking, changes dynamically at different phases of chronic HBV infection. In this study, we focused on the role of CCDC88A/GIV in HBV replication. In the liver tissues of chronically HBV-infected patients, HBV infection significantly enhanced CCDC88A/GIV expression, and increased endoplasmic reticulum (ER) stress and autophagosome formation without changing endosome formation. Additionally, colocalization of SHBsAg with early endosomes (30.2%) far exceeded that with autophagosomes (3.2%). In hepatoma cells, CCDC88A/GIV and its downstream proteins, DNM2 (dynamin 2; a CCDC88A/GIV effector), CLTC and RAB5A significantly enhanced HBV replication and endosome formation but inhibited autophagosome formation. Blocking endocytosis disrupted HBsAg trafficking to endosomes and caused its accumulation in the ER lumen, which triggered ER stress to initiate the unfolded protein response (UPR). Therefore, HBsAg trafficking into autophagosomes was increased, and the lysosomal activity and maturation, which was inhibited by HBV infection, were restored. Meanwhile, core particles were prevented from entering MVBs. CCDC88A/GIV and its other effector, GNAI3, decreased autophagic flux by enhancing the insulin-induced AKT-MTOR pathway, thereby inhibiting HBV antigens autophagic degradation. In conclusion, CCDC88A/GIV enhanced HBV replication by increasing endosomal trafficking and reducing autophagic degradation of HBV antigens, suggesting that CCDC88A/GIV-mediated endosomal trafficking plays an important role in HBV replication and progeny secretion.: ACTB: actin beta; AO: acridine orange; ATF6: activating transcription factor 6; CCDC88A/GIV: coiled-coil domain containing 88A; CLTC: clathrin heavy chain; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DNM2: dynamin 2; ER: endoplasmic reticulum; ERN1: endoplasmic reticulum to nucleus signaling 1; EIF2A: eukaryotic translation initiation factor 2A; FBS: fetal bovine serum; GNAI3: G protein subunit alpha i3; HBV: hepatitis B virus; HBV RIs: HBV replication intermediates; HBcAg: HBV core protein; HBsAg: HBV surface antigen; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MVBs: multivesicular bodies; MTOR: mechanistic target of rapamycin kinase; PDI: protein disulfide isomerase; PHH: primary human hepatocyte; pSM2: a HBV replication-competent plasmid; HSPA5/BIP: heat shock protein family A (Hsp70) member 5; SQSTM1/p62: sequestosome 1; siRNA: small interfering RNA; SEM: standard error of the mean; UPR: unfolded protein response.

摘要

乙型肝炎病毒 (HBV) 颗粒被认为是通过多泡体 (MVBs) 从肝细胞中分泌出来的;然而，在此过程之前的细胞运输机制仍然难以捉摸。据报道，CCDC88A/GIV 的表达参与了囊泡运输的多个方面，在慢性 HBV 感染的不同阶段动态变化。在本研究中，我们专注于 CCDC88A/GIV 在 HBV 复制中的作用。在慢性 HBV 感染患者的肝组织中，HBV 感染显著增强了 CCDC88A/GIV 的表达，增加了内质网 (ER) 应激和自噬体的形成，而不改变内体的形成。此外，SHBsAg 与早期内体 (30.2%) 的共定位远远超过与自噬体 (3.2%) 的共定位。在肝癌细胞中，CCDC88A/GIV 及其下游蛋白，DNM2(动力蛋白 2;CCDC88A/GIV 的效应物)、CLTC 和 RAB5A 显著增强了 HBV 的复制和内体的形成，但抑制了自噬体的形成。阻断内吞作用会破坏 HBsAg 向内体的运输，并导致其在内质网腔中积累，从而引发未折叠蛋白反应 (UPR)。因此，HBsAg 向自噬体的运输增加，而被 HBV 感染抑制的溶酶体活性和成熟得到恢复。同时，核心颗粒被阻止进入 MVBs。CCDC88A/GIV 和其另一个效应物 GNAI3 通过增强胰岛素诱导的 AKT-MTOR 通路增加了自噬通量，从而抑制了 HBV 抗原的自噬降解。总之，CCDC88A/GIV 通过增加内体运输和减少 HBV 抗原的自噬降解来增强 HBV 的复制，这表明 CCDC88A/GIV 介导的内体运输在 HBV 复制和后代分泌中起着重要作用。:ACTB:肌动蛋白β;AO:吖啶橙;ATF6:激活转录因子 6;CCDC88A/GIV:卷曲螺旋结构域 88A;CLTC:网格蛋白重链;CQ:氯喹;DAPI:4'，6-二脒基-2-苯基吲哚;DNM2:动力蛋白 2;ER:内质网;ERN1:内质网向核信号 1;EIF2A:真核翻译起始因子 2A;FBS:胎牛血清;GNAI3:G 蛋白亚单位 α i3;HBV:乙型肝炎病毒;HBV RIs:HBV 复制中间体;HBcAg:HBV 核心蛋白;HBsAg:HBV 表面抗原;MAP1LC3B/LC3B:微管相关蛋白 1 轻链 3β;MVBs:多泡体;MTOR:雷帕霉素靶蛋白激酶;PDI:蛋白质二硫键异构酶;PHH:原代人肝细胞;pSM2:HBV 复制有效的质粒;HSPA5/BIP:热休克蛋白家族 A (Hsp70) 成员 5;SQSTM1/p62:自噬体 1;p62;siRNA:小干扰 RNA;SEM:均数的标准误差;UPR:未折叠蛋白反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4349/8942511/7d208c148798/KAUP_A_1934271_F0009_OC.jpg
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本文引用的文献

1
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2
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3
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乙肝表面抗原劫持TANK结合激酶1以抑制I型干扰素并诱导早期自噬。
Cell Death Dis. 2025 Apr 15;16(1):304. doi: 10.1038/s41419-025-07605-0.
4
Amphisome plays a role in HBV production and release through the endosomal and autophagic pathways.双膜囊泡通过内吞体和自噬途径在乙肝病毒的产生和释放过程中发挥作用。
Hepatol Commun. 2025 Mar 13;9(4). doi: 10.1097/HC9.0000000000000654. eCollection 2025 Apr 1.
5
Bridging the gap: investigating the role of phosphorylation at the serine 129 site of α-synuclein in VAPB-PTPIP51 interactions.弥合差距：研究α-突触核蛋白丝氨酸129位点磷酸化在VAPB-PTPIP51相互作用中的作用。
Acta Neuropathol Commun. 2025 Feb 24;13(1):40. doi: 10.1186/s40478-025-01949-6.
6
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7
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4
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5
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Cell Microbiol. 2020 Feb;22(2):e13131. doi: 10.1111/cmi.13131. Epub 2019 Dec 4.
6
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7
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8
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9
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