Sheu S Y, Chen K L, Lee Y W, Lo S J
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, 11221, Republic of China.
Virology. 1996 Apr 1;218(1):275-8. doi: 10.1006/viro.1996.0191.
The large delta antigen (LDAg) of hepatitis D virus (HDV), which is similar to the small delta antigen (SDAg), except it has 19 additional amino acids and an isoprenylation signal at the C-terminus, is crucial for interacting with hepatitis B surface antigen (HBsAg) to form a mature 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 plasmids encoding deletion or isoprenylation-negative mutants of LDAg with a plasmid encoding HBsAg into human hepatoma cells, we demonstrated that (i) the isoprenylation-negative LDAg cannot be secreted, (ii) the coiled-coil domain-deleted LDAg retains the secretion capability, (iii) the isoprenylation-negative LDAg can neither cosecrete with isoprenylation-positive LDAg nor suppress its secretion, and (iv) an intermolecular interaction between LDAgs is unlikely required for secretion. A hypothetical model of empty HDV particle containing HBsAg with isoprenylated LDAgs, which are probably present in a singular form, was then proposed.
丁型肝炎病毒（HDV）的大δ抗原（LDAg）与小δ抗原（SDAg）相似，只是它在C末端多了19个氨基酸和一个异戊二烯化信号，这对于与乙型肝炎表面抗原（HBsAg）相互作用形成成熟的HDV病毒粒子至关重要。先前的研究表明，单独的LDAg而非SDAg能够与HBsAg相互作用形成空颗粒。然而，尚无证据表明LDAg的分子间相互作用对于形成空的HDV颗粒是否必要。通过将编码LDAg缺失或异戊二烯化阴性突变体的质粒与编码HBsAg的质粒共转染到人肝癌细胞中，我们证明：（i）异戊二烯化阴性的LDAg不能分泌；（ii）卷曲螺旋结构域缺失的LDAg保留分泌能力；（iii）异戊二烯化阴性的LDAg既不能与异戊二烯化阳性的LDAg共分泌，也不能抑制其分泌；（iv）分泌过程不太可能需要LDAg之间的分子间相互作用。随后提出了一个包含HBsAg以及可能以单一形式存在的异戊二烯化LDAg的空HDV颗粒的假设模型。
