Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. Dec 25, 2023; 12(5): 296-308
Published online Dec 25, 2023. doi: 10.5501/wjv.v12.i5.296
Perilipin2 inhibits the replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions
Chuang Wang, Xiao-Yun Gao, Mei Han, Meng-Chun Jiang, Xiao-Yi Shi, Chun-Wen Pu, Xuan Du
Chuang Wang, Xiao-Yi Shi, Graduate School, Graduate School of Dalian Medical University, Dalian 116000, Liaoning Province, China
Xiao-Yun Gao, Department of Geriatric, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Mei Han, Meng-Chun Jiang, Xuan Du, Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Chun-Wen Pu, Dalian Public Health Clinical Center, Dalian Municipal Research Institute for Public Health, Dalian 116001, Liaoning Province, China
Co-first authors: Chuang Wang and Xiao-Yun Gao.
Co-corresponding authors: Chun-Wen Pu and Xuan Du.
Author contributions: Du X and Gao XY designed the experiment and drafted the manuscript; Wang C performed the experiments; Du X and Wang C participated in the statistical analyses; Han M, Shi XY, and Jiang CM helped draft the manuscript; All authors have read and approved the final manuscript.
Institutional review board statement: The study has been approved by the Ethics Committee of Dalian Sixth People's Hospital. The privacy rights of human subjects were always respected during human experimentation, and informed consent was obtained prior to the experiment. The ethics program number is DLY/CB-IRB-026.
Institutional animal care and use committee statement: This study does not involve animal experiments.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xuan Du, PhD, Doctor, Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian 116023, Liaoning Province, China.
Received: September 11, 2023
Peer-review started: September 11, 2023
First decision: October 9, 2023
Revised: October 19, 2023
Accepted: November 30, 2023
Article in press: November 30, 2023
Published online: December 25, 2023

Chronic hepatitis B virus (HBV) infection is often associated with increased lipid deposition in hepatocytes. However, when combined with non-alcoholic fatty liver disease or hyperlipidemia, it tends to have a lower HBV deoxyribonucleic acid (DNA) load. The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood.


To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms.


1603 HBsAg-seropositive patients were included in the study. We first explored the relationship between patients' lipid levels, hepatic steatosis, and HBV DNA load. Also, we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro. By knocking down and overexpressing Plin2, we observed whether Plin2 regulates autophagy and HBV replication. By inhibiting both Plin2 and cellular autophagy under high lipid stimulation, we examined whether the Plin2-autophagy pathway regulates HBV replication.


The results revealed that serum triglyceride levels, high-density lipoprotein levels, and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group. Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load. Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAg-positive and HBeAg-negative groups. An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism. The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg, HBeAg, and HBV DNA load. Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins. Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy. Knocking down Plin2 and blocking autophagy with 3-methyladenine (3-MA) inhibited HBV DNA replication.


In conclusion, lipid metabolism is a significant factor affecting HBV load in patients with HBV infection. The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.

Keywords: Lipid metabolism, Chronic HBV infection, Nonalcoholic fatty liver, Plin2, Autophagy

Core Tip: Our data suggest that fatty acid stimulation inhibits hepatitis B virus (HBV) replication by upregulating Plin2 expression, inhibiting hepatocyte autophagy. This process associates with lipid metabolism, autophagy pathway, and HBV replication. Further study of lipid metabolism-Plin2-autophagy is important to understand HBV host interactions and pathogenesis better and suggests a possible route for treating patients with chronic HBV infection combined with nonalcoholic fatty liver disease.