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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


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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
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
著者: Bui, Thu Thuy
発行日: 2018年 9月20日
出版者: Microbiology Society
引用: Nagasaki University (長崎大学), 博士(医学) (2018-09-20)
抄録: 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.
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 / 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 / Citation: Journal of General Virology, 99(8), pp.1044-1057; 2018
キーワード: Dengue virus / NS4B / variants
URI: http://hdl.handle.net/10069/38586
ISSN: 00221317
DOI: 10.1099/jgv.0.001092
権利: © 2018 Microbiology Society
資料タイプ: Thesis or Dissertation
原稿種類: ETD
出現コレクション:110 学位論文

引用URI : http://hdl.handle.net/10069/38586

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