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Molecular and cellular biochemistry
Nov, 2022;477 (11): 2481-2491.

Hepatocyte steatosis inhibits hepatitis B virus secretion via induction of endoplasmic reticulum stress.

Qichuang Liu, Maoyuan Mu, Huan Chen, Guoyuan Zhang, Yanqing Yang, Jun Chu, Ying Li, Fangwan Yang, Shide Lin
Author Information
  1. Qichuang Liu: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  2. Maoyuan Mu: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  3. Huan Chen: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  4. Guoyuan Zhang: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  5. Yanqing Yang: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  6. Jun Chu: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  7. Ying Li: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  8. Fangwan Yang: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
  9. Shide Lin: Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China. Linshide6@hotmail.com. ORCID
PMID: 33983562 DOI: 10.1007/s11010-021-04143-z

Abstract

The effects of hepatocyte steatosis on hepatitis B virus (HBV) DNA replication and HBV-related antigen secretion are incompletely understood. The aims of this study are to explore the effects and mechanism of hepatocyte steatosis on HBV replication and secretion. Stearic acid (SA) and oleic acid (OA) were used to induce HepG2.2.15 cell steatosis in this study. The expressions of glucose-regulated protein 78 (GRP78), phosphorylation of protein kinase R-like endoplasmic reticulum (ER) kinase (p-PERK), and eukaryotic translation initiation factor 2α (p-eIF2α) were detected by Western blotting (WB). HBV DNA, HBsAg, and HBeAg in the supernatant were determined by real-time fluorescent polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Intracellular HBV DNA, HBsAg level, and HBV RNA were measured by real-time fluorescent PCR, WB, and real-time quantitative reverse transcriptase-PCR, respectively. The results showed that SA and OA significantly increased intracellular lipid droplets and triglyceride levels. SA and OA significantly induced GRP78, p-PERK, and p-eIF2α expressions from 24 to 72 h. 4-phenylbutyric acid (PBA) alleviated ER stress induced by SA. SA promoted intracellular HBsAg and HBV DNA accumulation; however, it inhibited the transcript of HBV 3.5 kb mRNA and S mRNA. The secretion of HBsAg and HBV DNA inhibited by SA or OA could be partially restored by pretreatment with PBA but not by inhibiting GRP78 expression with siRNA. Hepatocyte steatosis inhibits HBsAg and HBV DNA secretion via induction of ER stress in hepatocytes, but not via induction of GRP78.

Keywords

Endoplasmic reticulum stress HBVDNA HBsAg HepG2.2.15 cell Oleic acid Stearic acid

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Grants

  1. 81460124/Funds of China National Natural Science Foundation Project

MeSH Term

Hepatitis B virus
Hepatitis B Surface Antigens
Endoplasmic Reticulum Stress
DNA, Viral
Hepatocytes
Eukaryotic Initiation Factor-2
RNA, Messenger
Virus Replication

Chemicals

Hepatitis B Surface Antigens
DNA, Viral
Eukaryotic Initiation Factor-2
RNA, Messenger
Journal Article

Word Cloud

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