Hepatitis B virus inhibits apolipoprotein A5 expression through its core gene

Abstract

BackgroundHepatitis B virus (HBV) infection causes lipid metabolism disorders. Apolipoprotein A5 (ApoA5) is a new apolipoprotein family member that plays an important role in the regulation of lipid metabolism. The present study was to investigate the impact of HBV on ApoA5 expression and its regulatory mechanism.MethodsReverse transcription polymerase chain reaction (RT-PCR) and western blotting were used to measure ApoA5 mRNA and protein expression in HepG2 and HepG2.2.15 cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum ApoA5 levels in healthy individuals and HBV patients. HBV infectious clone pHBV1.3 or individual plasmids expressing the HBV genome was cotransfected with the ApoA5 promoter pGL3-Apo5-LUC plasmid into HepG2 cells to assess the luciferase activity. RT-PCR and western blotting methods were used to detect Apo5 mRNA and protein expression, respectively.ResultsThe ApoA5 mRNA and protein expression levels were decreased in HepG2.2.15 cells compared with the control HepG2 cells. The serum ApoA5 levels were 196.4 ± 28.7 μg/L in the healthy individuals and 104.5 ± 18.3 μg/L in the HBV patients, statistical analysis showed that the ApoA5 levels were significantly lower in HBV patients than in the healthy individuals (P < 0.05). pHBV1.3 and its core gene inhibited ApoA5 promoter activity and mRNA and protein expression in HepG2 cells.ConclusionHBV inhibits ApoA5 expression at both the transcriptional and translational levels through its core gene.

Current but not past hepatitis B virus infection is associated with a decreased risk of nonalcoholic fatty liver disease in the Chinese population: A case‐control study with propensity score analysis

“…Lower apolipoprotein B levels were found to be associated with a lower prevalence of NAFLD . Similarly, it has been suggested that HBV has an inhibitory effect on the secretion of apolipoprotein A5, a new member of the apolipoprotein family, in vivo and in vitro . It was found that knockdown of apolipoprotein A5 gene expression using small interfering RNA significantly decreased the intrahepatic triglyceride content .…”

“…48 Similarly, it has been suggested that HBV has an inhibitory effect on the secretion of apolipoprotein A5, a new member of the apolipoprotein family, in vivo and in vitro. 49 It was found that knockdown of apolipoprotein A5 gene expression using small interfering RNA significantly decreased the intrahepatic triglyceride content. 50 Furthermore, observational studies found that patients with current HBV infection had a decreased prevalence of hypertriglyceridemia and hypercholesterolaemia.…”

Hepatitis B virus inhibits the in vivo and in vitro synthesis and secretion of apolipoprotein C3

“…HepG2 cells were co-transfected with all of the individual plasmid eukaryotic expression vectors containing the HBV genome and the ApoC3 gene promoter pApoC3-Luc, respectively, pCMV-tag2B was set as the control [ 11 ]. The results showed that the HBX significantly down-regulated the promoter activity of ApoC3 gene (Fig.…”

“…Jiang W and Wang Y confirmed the regulatory effect of HBV on ApoA1 [ 10 , 16 ]. Our previous study also demonstrated the molecular mechanism of HBV inhibition of ApoB expression and found that HBV can inhibit the expression of ApoA5 [ 9 , 11 ]. In this study, we found that the expression levels of ApoC3 mRNA and protein in HepG2.2.15 cells were lower than those in HepG2 cells, which is consistent with the microarray results of Norton PA. We also found that the expression levels of the ApoC3 promoter, mRNA and protein were inhibited by the transfection of the HBV-infected clone pHBV1.3 and HBV X gene.…”

“…It was reported that HBV down-regulated the expression of ApoA1, ApoA5, ApoB and up-regulated the expression of ApoM [ 8 – 11 ].The main purpose of this study is to investigate the effect of HBV on the regulation of ApoC3 expression and its mechanism by in vivo and in vitro experiments.…”