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    請使用永久網址來引用或連結此文件: https://irlib.pccu.edu.tw/handle/987654321/41918


    題名: Tat-enhanced delivery of the C terminus of HDAg-L inhibits assembly and secretion of hepatitis D virus
    作者: 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)
    貢獻者: 化學系所
    關鍵詞: NUCLEAR EXPORT SIGNAL
    DELTA-VIRUS
    B-VIRUS
    FUSION PROTEINS
    MESSENGER-RNA
    LARGE FORM
    ANTIGEN
    REPLICATION
    CELLS
    IDENTIFICATION
    日期: 2018-02
    上傳時間: 2019-01-21 15:26:12 (UTC+8)
    摘要: 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.
    關聯: Antiviral Research卷 150, 頁 69 - 78 February 2018
    顯示於類別:[化學系所] 期刊論文

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