Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment

which is the type virus of the hepadnaviridae (hepatotropic DNA viruses). HBV consists of a nucleoprotein core containing a relatively small DNA genome (3,200 bp) surrounded by a protein capsid composed of the core protein, hepatitis B core antigen. The nucleocapsid is surrounded by an envelope in which the major protein component is the 226 amino acid hepatitis B surface antigen (HBsAg) which exists in nonglycosylated 24-kD (P24) and in N-glycosylated 27-kD (GP27) forms. In addition to being an envelope protein of the infectious virion, HBsAg is assembled into coreless, lipoprotein particles that are secreted from HBV infected cells and form the bulk of HBsAg in the circulation. These noninfectious lipoprotein particles occur in two morphological forms: 22-nm diameter particles which appear as spherical when negatively stained for EM and filamentous particles of the same diameter and variable length (Bayer et al., 1968; Robinson and Lutwick, 1976; Dane et al., 1970) . The "spherical" forms appear disk-like when visualized by cryoelectron microscopy and could represent fragments of the tubular forms (Huovila, A.-P. J., and S. D. Fuller, manuscript in preparation). The round 22-rim I-IBsAg particles isolated from the sera of HBV infected patients are complex macromolecular assemblies with a molecular weight between 2 and 4 • 106 (Dreesman et al., 1972; Kim and Tilles, 1973) , containing ~75 % protein, 25 % lipid, and N-linked carbohydrate (Gavilanes et al., 1981; Peterson, 1987) . One lipoprotein particle contains ~100 HBsAg polypeptide monomers (Aggerbeck and Peterson, 1985; Ganem and Varmus, 1987; Peterson, 1987) . I-IBsAg particles are unique among lipoproteins in that their structure is stabilized by extensive intermolecular disulphide crosslinking (Sukeno et al., 1972; Vyas et al., 1972; Imai et al., 1974; Peterson, 1987) . It is the site of formation of these extensive crosslinks which is the subject of this paper.