Membrane structure of the hepatitis B virus surface antigen particle

Expression of S protein, an envelope protein of hepatitis B virus, in the a bsence of other viral proteins, leads to the secretion of hepatitis B virus surface antigen (HBsAg) particles that are formed by budding from the endo plasmic reticulum membranes. The HBsAg particles produced by mouse fibrobla st cells show a unique lipid composition, with 1,2-diacyl glycerophosphocho line being the dominant component. The lipid organization of the HBsAg part icles was studied by measuring electron spin resonance (ESR) using various spin-labeled fatty acids, and the results were compared with a parallel stu dy on HVJ (Sendai virus) and vesicles reconstituted with total lipids of th e HBsAg particles (HBs-lipid vesicles). HVJ and the HBs-lipid vesicles show ed typical ESR spectra of lipids arranged in a lipid bilayer structure. In contrast, the ESR spectra obtained with the HBsAg particles showed that the movement of lipids in the particle is severely restricted and a typical im mobilized signal characteristic of tight lipid-protein interactions was als o evident. Phosphatidylcholine (PC) in the HBsAg particles was not exchange able by a PC-specific exchange protein purified from bovine liver, while ph ospholipase A(2) from Naja naja vemon was able to hydrolyze all the PC in t he particles. These analyses suggest that the lipids in the HBsAg particles are not organized in a typical lipid bilayer structure, but are located at the surface of the particles and are in a highly immobilized state. Based on these observations we propose a unique lipid assembly and membrane struc ture model for HBsAg particles.