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  1. 学位論文
  2. 博士論文(医学)
  3. 本文

Involvement of ribosomal protein L17 and Y-Box binding protein 1 in assembly of hepatitis C virus potentially via their interaction with the 3’ untranslated region of the viral genome

http://hdl.handle.net/10271/0002000461
http://hdl.handle.net/10271/0002000461
967c0106-31a5-40c7-9cdf-5c1689e94f00
名前 / ファイル ライセンス アクション
DT_989ronbun.pdf 論文本文 (1.4 MB)
license.icon
Item type 共通アイテムタイプ / Common item types(1)
公開日 2025-07-10
タイトル
タイトル Involvement of ribosomal protein L17 and Y-Box binding protein 1 in assembly of hepatitis C virus potentially via their interaction with the 3’ untranslated region of the viral genome
言語
言語 eng
キーワード
主題 hepatitis C virus
キーワード
主題 particle assembly
キーワード
主題 encapsidation
キーワード
主題 genome packaging
キーワード
主題 RPL17
キーワード
主題 YBX1
その他のタイトル
その他のタイトル リボソームタンパク質L17とYボックス結合タンパク質1はC型肝炎ウイルスの3'非翻訳領域との相互作用を介してウイルスのアセンブリに関与する
資源タイプ
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
著者 Liu, Jie

× Liu, Jie

en Liu, Jie
Hamamatsu University School of Medicine

ja ISNI 浜松医科大学 0000000089376696

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著者情報 リウ, ジエ

× リウ, ジエ

ja リウ, ジエ

zh-tw 刘, 杰

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書誌情報 en : Journal of Virology

巻 98, 号 7, p. e00522-24, 発行日 2024-06-20
出版者
出版者 American Society for Microbiology
権利
権利情報 Copyright 2024 American Society for Microbiology.
抄録
内容記述タイプ Abstract
内容記述 The 3′ untranslated region (3′UTR) of the hepatitis C virus (HCV) RNA genome, which contains a highly conserved 3′ region named the 3′X-tail, plays an essential role in RNA replication and promotes viral IRES-dependent translation. Although our previous work has found a cis-acting element for genome encapsidation within 3′X, there is limited information on the involvement of the 3′UTR in particle formation. In this study, proteomic analyses identified host cell proteins that bind to the 3′UTR containing the 3′X region but not to the sequence lacking the 3′X. Further characterization showed that RNA-binding proteins, ribosomal protein L17 (RPL17), and Y-box binding protein 1 (YBX1) facilitate the efficient production of infectious HCV particles in the virus infection cells. Using small interfering RNA (siRNA)-mediated gene silencing in four assays that distinguish between the various stages of the HCV life cycle, RPL17 and YBX1 were found to be most important for particle assembly in the trans-packaging assay with replication-defective subgenomic RNA. In vitro assays showed that RPL17 and YBX1 bind to the 3′UTR RNA and deletion of the 3′X region attenuates their interaction. Knockdown of RPL17 or YBX1 resulted in reducing the amount of HCV RNA co-precipitating with the viral Core protein by RNA immunoprecipitation and increasing the relative distance in space between Core and double-stranded RNA by confocal imaging, suggesting that RPL17 and YBX1 potentially affect HCV RNA-Core interaction, leading to efficient nucleocapsid assembly. These host factors provide new clues to understanding the molecular mechanisms that regulate HCV particle formation.
注記
内容記述 IMPORTANCE
Although basic research on the HCV life cycle has progressed significantly over the past two decades, our understanding of the molecular mechanisms that regulate the process of particle formation, in particular encapsidation of the genome or nucleocapsid assembly, has been limited. We present here, for the first time, that two RNA-binding proteins, RPL17 and YBX1, bind to the 3′X in the 3′UTR of the HCV genome, which potentially acts as a packaging signal, and facilitates the viral particle assembly. Our study revealed that RPL17 and YBX1 exert a positive effect on the interaction between HCV RNA and Core protein, suggesting that the presence of both host factors modulate an RNA structure or conformation suitable for packaging the viral genome. These findings help us to elucidate not only the regulatory mechanism of the particle assembly of HCV but also the function of host RNA-binding proteins during viral infection.
学位名
学位名 博士(医学)
学位の区分
内容記述 doctoral
学位の分野
内容記述 医学系研究科
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 13802
学位授与機関名 浜松医科大学
学位授与機関名 Hamamatsu University School of Medicine
学位授与年月日
学位授与年月日 2024-07-19
学位授与番号
学位授与番号 甲第989号
PISSN
収録物識別子 0022-538X
EISSN
収録物識別子 1098-5514
NII書誌ID (NCID)
収録物識別子 A00708779
PubMed番号 (PMID)
関連識別子 38899899
出版社DOI
関連識別子 https://doi.org/10.1128/jvi.00522-24
学位論文要旨/本文へのリンク
関連識別子 http://hdl.handle.net/10271/0002000241
関連名称 学位論文要旨
出版タイプ
出版タイプ VoR
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