Loading...
|
Please use this identifier to cite or link to this item:
https://irlib.pccu.edu.tw/handle/987654321/41918
|
| Title: | Tat-enhanced delivery of the C terminus of HDAg-L inhibits assembly and secretion of hepatitis D virus |
| Authors: | Huang, HC (Huang, Hsiu-Chen)
Lu, HF (Lu, Hsu-Feng)
Lai, YH (Lai, Yu-Heng)
Lee, CP (Lee, Chung-Pei)
Liu, HK (Liu, Hui-Kang)
Huang, C (Huang, Cheng) |
| Contributors: | 化學系所 |
| Keywords: | NUCLEAR EXPORT SIGNAL
DELTA-VIRUS
B-VIRUS
FUSION PROTEINS
MESSENGER-RNA
LARGE FORM
ANTIGEN
REPLICATION
CELLS
IDENTIFICATION |
| Date: | 2018-02 |
| Issue Date: | 2019-01-21 15:26:12 (UTC+8) |
| Abstract: | Hepatitis D virus (HDV) contains a single-stranded circular RNA genome that encodes two forms of hepatitis delta antigen (HDAg), the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L). The two proteins have an identical amino acid sequence, except that HDAg-L has a 19-amino-acid extension at the C terminus. The domain spanning amino acid residues 198-210 of the HDAg-L (HDAg-L(198-210)) contains a nuclear export signal (NES), which is important for the nuclear export of HDV ribonucleoprotein to the cytoplasm. In this study, we established a cell permeable TAT-HA-HDAg-L(198-210) fusion protein using an E. coli protein expression system, to determine its function during HDV infection. The cytotoxicity of the TAT-HA-HDAg-L(198-210) fusion protein was investigated using an MTT assay, while a GST pull-down assay revealed that the TAT-HA-HDAg-L (198-210) fusion protein interfered with the interaction between HDAg-L and clathrin heavy chain (CHC). In addition, the cellular distribution of HDAg-L, in the presence of HBsAg, was observed by immunofluorescence staining and the TAT-HA-HDAg-L(198-210) fusion protein was found to impede the nuclear export of HDAg-L. Furthermore, assembly of HDV virus-like particles (VLPs) was decreased by the expression of the TAT-HDAg-L (198-210) fusion protein. The TAT-HA-HDAg-L(198-210) fusion protein also inhibited virus particle assembly and HDV secretion in a mouse model. These results suggest that the TAT-HA-HDAg-L(198-210) fusion protein inhibits the nuclear export of HDAg-L and competes with the C terminus of HDAg-L for interaction with CHC, and may have potential as a therapeutic agent for HDV infection. |
| Relation: | Antiviral Research卷 150, 頁 69 - 78 February 2018 |
| Appears in Collections: | [Department of Chemistry & Graduate Institute of Applied Chemistry ] journal articles
|
Files in This Item:
| File |
Description |
Size | Format | |
|---|
| index.html | | 0Kb | HTML | 192 | View/Open |
|
All items in CCUR are protected by copyright, with all rights reserved.
|
