{"created":"2023-07-27T06:51:02.598636+00:00","id":44291,"links":{},"metadata":{"_buckets":{"deposit":"85565955-7f57-4ea0-aaed-af83ca815fdf"},"_deposit":{"created_by":18,"id":"44291","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44291"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044291","sets":["2812:2813:2827"]},"author_link":["74055","93"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"14p.","bibliographicVolumeNumber":"2005-2006","bibliographic_titles":[{"bibliographic_title":"平成18(2006)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2006 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"これまでにHCV-IRES発現細胞RCF-26を用いてHCV-IRES関連因子の中でLa,PTB,eIF2 gamma,PSMA7がHCV-IRES活性に重要な働きを有していることを示した。本研究ではHCVレプリコンを用いて、これらの翻訳因子がHCVの複製に与える影響を検討した。siRNAを用いて各翻訳因子の発現を特異的に抑制した場合、EMCV-IRESを有する従来型HCVレプリコン(NNeowt)の複製は抑制されなかったが、HCV-IRESのみを有する新たに構築したHCVレプリコン(MH14C)の複製は著明に抑制された。従ってこれらの翻訳因子の抑制はHCV-IRES活性の低下を介して、HCVの複製を抑制したものと考えられる。興味深いことに、実際のC型慢性肝炎肝組織におけるこれらの翻訳因子の発現とHCVの複製との関連を検討すると、La,eIF2 gamma,PSMA,PCBP2の発現が、肝組織内のHCV-RNAと有意に相関することが明らかになった。マイクロアレイを用いた正常肝18例、C型慢性肝炎肝組織37例の肝組織遺伝子発現プロファイル解析ではこれらの遺伝子はC型慢性肝炎肝組織で誘導される一群の遺伝子クラスターに群別された。さらにLaの発現制御を検討すると、LaはHCVタンパク自身の発現によって誘導されることが明らかとなった。Laプロモーター領域をクローニングし、ルシフェラーゼ・レポーターアッセイにて検討すると、HCVのあるタンパクが、Laプロモーターを活性化していることが明らかとなった。以上より、Laは細胞周期亢進によっても誘導されるほか、HCV感染そのものによっても誘導されることが明らかとなった。","subitem_description_type":"Abstract"},{"subitem_description":"Background and aim : Translation of the hepatitis C virus (HCV) is mediated by an internal ribosome entry site (IRES). Many translation initiation factors interact with HCV IRES; however, the functional relevance of these factors for the translation and replication of HCV has not been clarified. Methods : Two different subgenomic HCV replicons, NNeo/3-5B and MH14C, were used. NNeo/3-5B consists of an HCV replicon with a standard structure in which NS3-NS5 was translated by encephalomyocarditis (EMCV) IRES. MH14C is an HCV replicon with a modified structure in which EMCV IRES was replaced with HCV IRES. Of 14 translation initiation factors suppressed by antisense oligodeoxynucleotides or siRNA, La protein, PTB, eIF3 p170, eIF2 gamma, and PSMA 7 affected HCV IRES activity and the replication of MH14C. However, these factors did not affect EMCV IRES activity and the replication of NNeo/3-5B. La protein, eIF2 gamma, and PSMA7 were significantly correlated with HCV RNA in the liver of 37 patients with chronic hepatitis C (CH-C). Gene expression profiling using a cDNA microarray revealed these initiation factors were induced in CH-C and clustered in a group of genes representing inflammation, DNA repair and stress responses. One of the HCV coding proteins, NS5A, activated the La protein promoter and the interferon sensitivity-determining region in NS5A was responsible for the activation. Conclusions: HCV replication was highly dependent on translation initiation factors that were induced in tissue lesions of CH-C. The induction of La protein by the HCV protein NS5A might support the replication and persistent infection of HCV.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:17591036, 研究期間(年度):2005-2006","subitem_description_type":"Other"},{"subitem_description":"出典：「C型肝炎ウイルス増殖に関わる宿主因子の同定とその肝病態における役割」研究成果報告書　課題番号17591036\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00050633","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医薬保健研究域保健学系"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=00272980"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=00272980","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591036/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591036/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17591036/175910362006kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17591036/175910362006kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-04-26"}],"displaytype":"detail","filename":"ME-PR-HONDA-M-kaken 2007-14p.pdf","filesize":[{"value":"563.6 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-HONDA-M-kaken 2007-14p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44291/files/ME-PR-HONDA-M-kaken 2007-14p.pdf"},"version_id":"9ac1ffac-3cdb-41c8-85ba-b4e1fbd062e6"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"C型肝炎ウイルス増殖に関わる宿主因子の同定とその肝病態における役割","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"C型肝炎ウイルス増殖に関わる宿主因子の同定とその肝病態における役割"},{"subitem_title":"Identification of host factors required for HCV-IRES activity and their physiological roles in liver disease","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2827"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-04-26"},"publish_date":"2018-04-26","publish_status":"0","recid":"44291","relation_version_is_last":true,"title":["C型肝炎ウイルス増殖に関わる宿主因子の同定とその肝病態における役割"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:34:20.288765+00:00"}