PMID- 33370716
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20211204
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 131
DP  - 2021 Feb
TI  - Apolipoprotein H drives hepatitis B surface antigen retention and endoplasmic 
      reticulum stress during hepatitis B virus infection.
PG  - 105906
LID - S1357-2725(20)30223-5 [pii]
LID - 10.1016/j.biocel.2020.105906 [doi]
AB  - BACKGROUND: Apolipoprotein H (APOH), also known as beta2-glycoprotein I 
      (beta2-GPI), is an acute phase protein in hepatitis B virus (HBV) infection and 
      binds to hepatitis B surface antigen (HBsAg) with high-affinity. APOH expression 
      is upregulated by HBV and the large surface protein (LHBs), but also elevated in 
      HBV-related hepatoma cells. Previous studies show that intracellular retention of 
      HBsAg induces endoplasmic reticulum (ER) stress, a key driver of hepatocyte 
      damage during chronic liver injury, but the mechanisms are unclear. We 
      hypothesize that APOH mediates HBV-induced ER stress through increased retention 
      of HBsAg. METHODS: VR-APOH-myc and VR-LHBs-flag plasmids were constructed by PCR 
      using pcDNA3.1(-)-APOH or an HBV expression vector, respectively. APOH and ER 
      stress markers were examined at protein and mRNA levels by Western Blot or 
      RT-qPCR. HBsAg titer was assayed by ELISA. RNA-seq was performed to elucidate the 
      transcriptional impact of APOH manipulation in HBV-producing cells (HepG2.2.15 
      cells). RESULTS: We found that HBV upregulates APOH expression in 293 T cells, 
      and APOH overexpression subsequently inhibits secretion of HBsAg. Next, we show 
      that LHBs overexpression in conjunction with APOH leads to ER stress in 293 T 
      cells, as evidenced by production of the binding immunoglobulin protein (BiP) and 
      C/EBP homologous protein (CHOP), as well as increased splicing of X-box binding 
      protein 1 (XBP1). We further observed that loss of beta2-GPI reduced CHOP 
      expression in HepG2.2.15 cells, while beta2-GPI overexpression enhanced CHOP 
      production. CONCLUSION: The interaction of beta2-GPI and HBV initiates ER stress 
      through driving intracellular retention of HBsAg and activates the UPR.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Liu, Yaming
AU  - Liu Y
AD  - Department of Gastroenterology and Hepatology, Xiamen University Zhongshan 
      Hospital, Xiamen, Fujian Province, 361001, China; Department of Digestive 
      Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province, 361001, 
      China.
FAU - Maiers, Jessica L
AU  - Maiers JL
AD  - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, 
      55902, USA.
FAU - Rui, Yajuan
AU  - Rui Y
AD  - First Hospital of Jilin University, Changchun, Jilin Province, 132001, China.
FAU - Jiang, Xiaoming
AU  - Jiang X
AD  - First Hospital of Jilin University, Changchun, Jilin Province, 132001, China.
FAU - Guleng, Bayasi
AU  - Guleng B
AD  - Department of Gastroenterology and Hepatology, Xiamen University Zhongshan 
      Hospital, Xiamen, Fujian Province, 361001, China; Department of Digestive 
      Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province, 361001, 
      China.
FAU - Ren, Jianlin
AU  - Ren J
AD  - Department of Gastroenterology and Hepatology, Xiamen University Zhongshan 
      Hospital, Xiamen, Fujian Province, 361001, China; Department of Digestive 
      Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province, 361001, 
      China. Electronic address: Ren.Jianlin@outlook.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201226
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (DDIT3 protein, human)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (L protein, hepatitis B virus)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (XBP1 protein, human)
RN  - 0 (beta 2-Glycoprotein I)
RN  - 147336-12-7 (Transcription Factor CHOP)
SB  - IM
MH  - Endoplasmic Reticulum/*genetics/immunology/virology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*genetics/immunology
MH  - Gene Expression Regulation
MH  - HEK293 Cells
MH  - Heat-Shock Proteins/genetics/immunology
MH  - Hep G2 Cells
MH  - Hepatitis B Surface Antigens/*genetics/immunology
MH  - Hepatitis B virus/*genetics/immunology
MH  - Host-Pathogen Interactions/*genetics/immunology
MH  - Humans
MH  - Plasmids/chemistry/metabolism
MH  - Protein Binding
MH  - Signal Transduction
MH  - Transcription Factor CHOP/genetics/immunology
MH  - Transfection
MH  - Viral Envelope Proteins/genetics/immunology
MH  - X-Box Binding Protein 1/genetics/immunology
MH  - beta 2-Glycoprotein I/*genetics/immunology
OTO - NOTNLM
OT  - Endoplasmic reticulum stress (ER stress)
OT  - Hepatitis B surface antigen (HBsAg)
OT  - Hepatitis B virus (HBV)
OT  - beta2-glycoprotein I (beta2-GPI)
EDAT- 2020/12/29 06:00
MHDA- 2021/09/01 06:00
CRDT- 2020/12/28 20:10
PHST- 2020/06/06 00:00 [received]
PHST- 2020/12/03 00:00 [revised]
PHST- 2020/12/09 00:00 [accepted]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2020/12/28 20:10 [entrez]
AID - S1357-2725(20)30223-5 [pii]
AID - 10.1016/j.biocel.2020.105906 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2021 Feb;131:105906. doi: 10.1016/j.biocel.2020.105906. 
      Epub 2020 Dec 26.