Abstract

More than 90% of lipids of hepatitis B virus surface antigen (HBsAg) particles produced by two human hepatoma cell lines (huGK-14 and PLC/PRF/5) were composed of phospholipids, with phosphatidylcholine being the dominant component, accounting for more than 80% of total membrane lipids. Analysis of subclass compositions of phospholipids of HBsAg particles and the host cell lines revealed that 1,2-diacyl glycerophosphocholine was preferentially incorporated into the membrane of the HBsAg particles, although both host cell lines contained extremely high concentrations (more than 60% of total phospholipids) of ether-linked phospholipids. Phospholipids of other hepatoma cell lines (HuH-7, Hep-G2, and huL-1) which were not associated with hepatitis B virus (HBV) infection, were composed mostly of 1,2-diacylglycerophospholipids. Activities of dihydroxyacetone-phosphate acyltransferase, which is known to be an obligatory enzyme in ether lipid biosynthesis, were found to be elevated by three- to fourfold in both huGK-14 and PLC/PRF/5 cells compared to those of other hepatoma cell lines. The results suggest a possible relationship between HBV-induced hepatocellular carcinogenesis and the drastic change in the metabolism of membrane phospholipids.

Highlights

  • More than 90% of lipids of hepatitis B virus surface antigen (HBsAg) particles produced by two human hepatoma cell lines were composed of phospholipids, with phosphatidylcholine being the dominant component, accounting for more than 80% of total membrane lipids

  • The HBsAg particles produced by the human hepatoma cell lines resembled the HBsAg particles from patient plasma in morphology, physical characteristics, and protein composition [12, 37], certain differences in lipid composition were observed between cultured cell-derived and patient plasma-derived HBsAg particles

  • Electron microscopic analysis of the liver explants from infected patients and that of cultured cell lines that had been stably transformed with the S gene of hepatitis B virus (HBV) have indicated that the assembly and packing of HBsAg particles occur in the endoplasmic reticulum (ER) and the mature HBsAg particles are secreted via the vesicular pathway [38, 39]

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Summary

Introduction

More than 90% of lipids of hepatitis B virus surface antigen (HBsAg) particles produced by two human hepatoma cell lines (huGK-14 and PLC/PRF/5) were composed of phospholipids, with phosphatidylcholine being the dominant component, accounting for more than 80% of total membrane lipids. Phospholipids of other hepatoma cell lines (HUH-7,Hep-G2, and huL-1) which were not associated with hepatitis B virus (HBV) infection, were composed mostly of 1,2-diacylglycerophospholipidsA. Lipid composition of hepatitis B virus surface antigen particles and the particle-producing human hepatoma cell lines. During the chronic carrier state or the acute phase of the virus infection, large quantities of hepatitis B surface antigen (HBsAg) are secreted into the bloodstream. The study of the comparative lipid analyses of paramyxoviruses, myxoviruses, rhabdoviruses, and togaviruses showed that the composition of the viral lipids generally resembled the lipid composition of its host cell plasma membrane [5,6,7].

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