D型肝炎病毒之小型 Delta 抗原與 DNA- 依賴性 RNA 聚合酶 I 之交互作用

Interactions between Small Delta Antigen and DNA-dependent RNA Polymerase I

賴昱衡(Yu-Heng Lai)

指導教授 ： 張明富

國立臺灣大學/醫學院/生物化學暨分子生物學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.02125

摘要

D 型肝炎病毒 (hepatitis delta virus, HDV) 為一具有外套之球狀病毒顆粒，外套蛋白質由 B 型肝炎病毒表面抗原所組成，其內部組成為一單股環狀長約 1.7 kb 之 RNA 及其所轉譯之 delta 抗原。Delta 抗原有兩種：大型 delta 抗原 (HDAg-L，約為27 kDa) 及小型 delta 抗原 (HDAg-S，約為24 kDa)。比較胺基酸序列，發現大型 delta 抗原在 C 端比小型 delta 抗原多出 19 個胺基酸。
先前的研究指出，HDV RNA 之 mRNA 的轉錄是由宿主細胞中的 RNA pol II 所進行，其 mRNA 的轉錄會受到

關鍵字

小型 Delta 抗原 ； D型肝炎

並列摘要

Hepatitis delta virus (HDV) is a spherical virus particle with envelope. HDV is a satellite virus of hepatitis B virus, it contains hepatitis B surface antigens essential for viral infection. The viral particle possesses a 1.7 kb single-stranded circular RNA genome that is replicated by RNA-dependent RNA polymerase via a double rolling circle mechanism. A 0.8 kb mRNA encoding the hepatitis delta antigen (HDAg) is also generated during the viral replication. There are two forms of delta antigen, the small HDAg (HDAg-S, 24 kD) and the large HDAg (HDAg-L, 27 kD). Previsous studies indicate that host DNA-dependent RNA polymerase II (RNA pol II) is involved in the synthesis of the full length genomic RNA and mRNA of HDV. However, evidences suport that other cellular RNA polymerases are involved in the synthesis of HDV antigenomic RNA. At the early stage of viral replication, HDAg-S is localized at the nucleolus and binds to nucleolus proteins nucleolin and B23, suggesting that nucleolus-localized RNA pol I is a potential candidate for the synthesis of HDV antigenomic RNA.RNA polymerase I polypeptide A (RPA194) is the largest subunit in RNA pol I complex. It is responsible for ribosomal RNA transcription elongation. In this study, interaction between RPA194 and HDAg-S were indicated by co-immunoprecipitation. In addition, GST pull-down assay further demonstrated that the RPA194 constant region fragment a interacted with His-tagged HDAg-S. A reporter plamid were generated to examine the effect of HDAg-S on the rDNA promoter activity. The result demonstrated that HDAg-S inhibits the synthesis of rRNA. Mechanisms involved in the RNA pol I-mediated replication of HDV antigenomic RNA remains to be elucidated.

並列關鍵字

Small Delta Antigen ； HDV ； RNA polymerase I

參考文獻

2. Rizzetto, M., Canese, M. G., Gerin, J. L., London, W. T., Sly, D. L., and Gerin, R. H. (1980) Delta agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees. Proc. Natl. Acad. Sci. USA., 77, 6124-6128.

4. Bergman, K., and Gerin, J. (1986) Antigens of hepatitis delta virus in the liver and serum of human and animals. J. Infect. Dis., 154, 702-706.

1. Bonino, F., Heermann, K. H., Rizzetto, M., and Gerlich, W. H. (1986) Hepatitis delta virus: protein composition of delta antigen and its hepatitis D virus-derived envelope. J. Virol., 58, 945-950.

3. Sureau, C., Moriarty, A. M., Thornton, G. B., Lanford, R. E. (1992) Production of infectious hepatitis delta virus in vitro and neutralization with antibodies directed against hepatitis B virus pre-S antigen. J. Virol., 66, 1241-1245.

5. Weiner, A. J., Choo, Q. L., Wang, K. S., Govindarajan S., Redeker, A., Gerin, J. L., and Houghton, M. (1988) A single antigenomic open reading frame of hepatitis delta virus encode the epitope(s) of both hepatitis delta antigen polypeptides p24