NO INTERMOLECULAR INTERACTION BETWEEN THE LARGE HEPATITIS-DELTA ANTIGENS IS REQUIRED FOR THE SECRETION WITH HEPATITIS-B SURFACE-ANTIGEN - AMODEL OF EMPTY HDV PARTICLE

The large delta antigen (LDAg) of hepatitis D virus (HDV), which is si milar to the small delta antigen (SDAg), except it has 19 additional a mino acids and an isoprenylation signal at the C-terminus, is crucial for interacting with hepatitis B surface antigen (HBsAg) to form a mat ure virion of HDV. Previous studies indicated that the LDAg alone, but not SDAg, can interact with HBsAg to form an empty particle. However, no evidence yet shows whether the intermolecular interaction of LDAg is necessary for forming an empty HDV particle. By cotransfection of p lasmids encoding deletion or isoprenylation-negative mutants of LDAg w ith a plasmid encoding HBsAg into human hepatoma cells, we demonstrate d that (i) the isoprenylation-negative LDAg cannot be secreted, (ii) t he coiled-coil domain-deleted LDAg retains the secretion capability, ( iii) the isoprenylation-negative LDAg can neither cosecrete with isopr enylation-positive LDAg nor suppress its secretion, and (iv) an interm olecular interaction between LDAgs is unlikely required for secretion. A hypothetical model of empty HDV particle containing HBsAg with isop renylated LDAgs, which are probably present in a singular form, was th en proposed. (C) 1996 Academic Press, Inc.