A frameshift mutation in the pre-S region of the human hepatitis B virus genome allows production of surface antigen particles but eliminates binding to polymerized albumin.
The coding region for the major polypeptide (p24S) of hepatitis B surface antigen (HBsAg) is preceded by an in-phase open reading frame termed pre-S. The coding potential of the pre-S region was examined in mouse L cells transformed with cloned hepatitis B virus DNA. Such cells produce three HBsAg-related polypeptides of Mr 24,000, 27,000, and 35,000 organized into complex particles of 22 nm diameter. These HBsAg particles bind to polymerized human albumin, but not to polyalbumins of several other species. In contrast, cells transformed with hepatitis B virus DNA bearing a frameshift mutation near the 3' end of the pre-S region secrete immunoreactive HBsAg particles containing only the 24,000 and 27,000 Mr species. These mutant particles, which lack the 35,000 Mr species, are unable to bind polymerized human albumin. These studies indicate that the pre-S region encodes the 35,000 Mr species, that this product accounts for the known polyalbumin-binding activity of HBsAg but is not required for assembly and secretion of HBsAg 22-nm particles, and that the major polypeptide of HBsAg is not derived primarily by cleavage of larger precursors encoded by the pre-S region.
D004279:DNA, Viral / Q000235:genetics; D005786:Gene Expression Regulation; D005814:Genes, Viral; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D007739:L Cells; D046911:Macromolecular Substances; D008970:Molecular Weight; D012709:Serum Albumin / Q000378:metabolism; D000075462:Serum Albumin, Human; D013329:Structure-Activity Relationship; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics*
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D046911:Macromolecular Substances; D012709:Serum Albumin; D014764:Viral Proteins; C032137:polyalbumin; D000075462:Serum Albumin, Human