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A single amino acid substitution in the NS4B protein of Dengue virus confers enhanced virus growth and fitness in human cells in vitro through IFN-dependent host response
http://hdl.handle.net/10069/38586
http://hdl.handle.net/10069/38586800b6b15-499b-48e9-8407-ce7bbf91921c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ISYK1098_Bui.pdf (2.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-06-19 | |||||
| タイトル | ||||||
| タイトル | A single amino acid substitution in the NS4B protein of Dengue virus confers enhanced virus growth and fitness in human cells in vitro through IFN-dependent host response | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Dengue virus | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | NS4B | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | variants | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 著者 |
Bui, Thu Thuy
× Bui, Thu Thuy |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Dengue virus (DENV) replication between mosquito and human hosts is hypothesized to be associated with viral determinants that interact in a differential manner between hosts. However, the understanding of inter-host viral determinants that drive DENV replication and growth between hosts is limited. Through the use of clinical isolates, we identified an amino acid variation of Ala, Met and Val at position 116 of DENV-1 NS4B. While the proportion of virus with the NS4B-116V variant remained constantly high in serial passages in a mosquito cell line, populations of the NS4B-116M and NS4B-116A variants became dominant after serial passages in mammalian cell lines. Using recombinant DENV-1 viruses, the Val to Ala or Met alteration at position NS4B-116 (rDENV-1-NS4B-116A and rDENV-1-NS4B-116M) resulted in enhanced virus growth in human cells in comparison to the clone with Val at NS4B-116 (rDENV-1-NS4B-116V). However, the reverse phenomenon was observed in a mosquito cell line. Additionally, in a human cell line, differential levels of IFN-α/β and IFN-stimulated gene expressions (IFIT3, IFI44L, OAS1) suggested that the enhanced viral growth was dependent on the ability of the NS4B protein to hamper host IFN response during the early phase of infection. Overall, we identified a novel and critical viral determinant at the pTMD3 of NS4B region that displayed differential effects on DENV replication and fitness in human and mosquito cell lines. Taken together, the results suggest the importance of the NS4B protein in virus replication and adaptation between hosts. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第1098号 学位授与年月日:平成30年9月20日 | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Author: Thuy Thu Bui, Meng Ling Moi, Takeshi Nabeshima, Taichiro Takemura, Trang Thu Nguyen, Linh Ngoc Nguyen, Hang Thi Thu Pham, Thi Thu Thuy Nguyen, Dao Huy Manh, Shyam Prakash Dumre, Shusaku Mizukami, Kenji Hirayama, Shigeru Tajima, Mai Thi Quynh Le, Kiyoshi Aoyagi, Futoshi Hasebe and Kouichi Morita | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Citation: Journal of General Virology, 99(8), pp.1044-1057; 2018 | |||||
| 書誌情報 |
Journal of General Virology 巻 99, 号 8, p. 1044-1057, 発行日 2018-09-20 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 00221317 | |||||
| EISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 14652099 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1099/jgv.0.001092 | |||||
| 権利 | ||||||
| 権利情報 | c 2018 Microbiology Society | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| その他のタイトル | ||||||
| その他のタイトル | デングウイルス非構造タンパク質NS4Bの一残基変異はヒト細胞においてインターフェロンの応答を抑制しウイルス増殖および適合性を増強する | |||||
| 出版者 | ||||||
| 出版者 | Microbiology Society | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17301 | |||||
| 学位授与機関名 | Nagasaki University (長崎大学) | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2018-09-20 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲医歯薬第1098号 | |||||
| 学位の種類 | ||||||
| 値 | 課程博士 | |||||
| 引用 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Nagasaki University (長崎大学), 博士(医学) (2018-09-20) | |||||
