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

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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.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was supported by the Funds of China National Natural Science Foundation Project (81160067/H0318, 81460124).

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  1. Qichuang Liu and Maoyuan Mu contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China

    Qichuang Liu, Maoyuan Mu, Huan Chen, Guoyuan Zhang, Yanqing Yang, Jun Chu, Ying Li, Fangwan Yang & Shide Lin

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Contributions

SL conceived and designed the study and critically revised the manuscript. QL, MM, HC, and GZ performed the experiments, analyzed the data, and drafted the manuscript. JC, YY, YL, and FY participated in study design, study implementation, and manuscript revision. All authors read and approved the final manuscript.

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Correspondence to Shide Lin.

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Liu, Q., Mu, M., Chen, H. et al. Hepatocyte steatosis inhibits hepatitis B virus secretion via induction of endoplasmic reticulum stress. Mol Cell Biochem 477, 2481–2491 (2022). https://doi.org/10.1007/s11010-021-04143-z

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