https://scholars.lib.ntu.edu.tw/handle/123456789/545866
標題: | Isoprenylation of Large Hepatitis Delta Antigan Is Necessary but Not Sufficient for Hepatitis Delta Virus Assembly | 作者: | Lee, Cha-Ze PEI-JER CHEN Lai M.M.C. DING-SHINN CHEN |
公開日期: | 1994 | 卷: | 199 | 期: | 1 | 起(迄)頁: | 169-175 | 來源出版物: | Virology | 摘要: | Hepatitis delta virus (HDV) encodes two proteins, the small hepatitis delta antigan (SHDAg) and large hepatitis delta antigen (LHDAg). Both proteins are identical except for the presence of additional 19 amino acids at the C terminus of LHDAg. While SHDAg is required for HDV RNA replication, LHDAg inhibits replication and is required together with hepatitis B surface antigen for the assembly of HDV. The C-terminal last 4 amino acids of LHDAg (Cys-Arg-Pro-Gln) is an isoprenylation motif. It has previously been shown that the mutation of the Cys inhibited the assembly of HDV. In order to discern whether this effect is due to change of amino acid residue or abolition of isoprenylation, we constructed several LHDAg mutants of the terminal three amino acid residues and tested their abilities to be packaged with HBsAg by cotransfection experiments. We also made GST-fusion proteins of these mutants and tested their abilities to be isoprenylated in rabbit reticulocyte lysate system. We found that some, but not all, of the substitutions of the amino acid residues other than the Cys also inhibited isoprenylation and that the status of isoprenylation of these mutant proteins correlated well with their abilities to be packaged with HBsAg into virions. This result indicates that isoprenylation, rather than the primary amino acid sequence, is required for LHDAg packaging. Furthermore, we found that the attachment of an isoprenylation motif to SHDAg did not enable it to be packaged with HBsAg and that the deletions of any 5 amino acids in the last 15 amino acids (amino acids 196 to 210) unique to the LHDAg abolished the packaging ability. In contrast, the deletion of 33 amino acids (amino acids 163 to 195) upstream of the last C-terminal 19 amino acids of LHDAg did not interfere with its packaging ability. Therefore, we conclude that the 15 amino acids upstream of the isoprenylation site of LHDAg are also essential for HDV assembly, and a large portion of the alleged C-terminal Pro/Gly-rich region (amino acids 146 to 195) is not required for the assembly process. ? 1994 Academic Press. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028300412&doi=10.1006%2fviro.1994.1109&partnerID=40&md5=fc511f9b5b7cf1d0797b28647e9f2d42 https://scholars.lib.ntu.edu.tw/handle/123456789/545866 |
ISSN: | 0042-6822 | DOI: | 10.1006/viro.1994.1109 | SDG/關鍵字: | virus antigen; article; delta agent hepatitis; human; human cell; priority journal; protein analysis; protein function; virus assembly; Amino Acid Sequence; Antigens, Viral; Cell Line; Hepatitis delta Antigens; Hepatitis Delta Virus; Human; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Isoprenylation; Support, Non-U.S. Gov't |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。