ウイルス感染現象における宿主細胞コンピテンシーの分子基盤

• Project Area: Molecular basis of host cell competency in virus infection
• Project/Area Number: 24115001
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Research Institution: University of Tsukuba
• Principal Investigator: 永田 恭介 筑波大学, 学長 (40180492)
• Co-Investigator(Kenkyū-buntansha): 脇田 隆字 国立感染症研究所, 副所長, 副所長 (40280789) ; 藤田 尚志 京都大学, ウイルス研究所, 教授 (10156870) ; 柳 雄介 九州大学, 医学研究院, 教授 (40182365) ; 小池 智 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 参事研究員 (30195630) ; 夏目 徹 国立研究開発法人産業技術総合研究所, 創薬分子プロファイリング研究センター, 研究員 (00357683) ; 佐々木 顕 総合研究大学院大学, 先導科学研究科, 教授 (90211937)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Project Status: Granted(Fiscal Year 2016)
• Budget Amount: ¥53,950,000 (Direct Cost : ¥41,500,000、Indirect Cost : ¥12,450,000); Fiscal Year 2016 : ¥15,600,000 (Direct Cost : ¥12,000,000、Indirect Cost : ¥3,600,000); Fiscal Year 2015 : ¥10,400,000 (Direct Cost : ¥8,000,000、Indirect Cost : ¥2,400,000); Fiscal Year 2014 : ¥12,220,000 (Direct Cost : ¥9,400,000、Indirect Cost : ¥2,820,000); Fiscal Year 2013 : ¥10,400,000 (Direct Cost : ¥8,000,000、Indirect Cost : ¥2,400,000); Fiscal Year 2012 : ¥5,330,000 (Direct Cost : ¥4,100,000、Indirect Cost : ¥1,230,000)
• Keywords: ウイルス / 感染症 / 数理科学 / プロテオミクス / ポストゲノム / 感染コンピテンシー / 病原性発現 / 宿主特異性 / 宿主因子 / 許容性 / 共同研究インターンシップ / 感染防御

Outline of Annual Research Achievements

本研究は、総括班として、領域の研究推進を支援し、新たな研究概念の創出を支援することを目的とする。最終的には、病原性発現に帰結する宿主特異的なウイルス複製とそれに対抗する宿主防御メカニズムとの拮抗の分子基盤を理解し、ウイルス増殖の許容性／非許容性に繋がるウイルス側と宿主側の特性（感染コンピテンシー）を明らかにし、扱うウイルスを越えて、共通概念を抽出する研究を支援し、そのための異分野協業を推進する。
本年度では、１．ニューウェルシティ湯河原および筑波大学東京キャンパスにて、総括班会議を開催し、本領域の方向性と研究方針を議論した。２．ホームページを運営し、領域の活動を広報した。３．ニューウェルシティ湯河原および筑波大学東京キャンパスにて、第6回、第7回領域会議を開催した。４．共同研究インターンシップとして、1件の共同研究を支援した。５．ウイルス学キャンプ in 湯河原、ウイルス学若手学会、淡路島感染症フォーラムを支援し、国外の研究者ウイルス領域外の若手研究者との人的交流のサポートを行った。６．領域内の研究者を対象として、1件の国際学会発表を支援した。７．社会連携活動「高校生のためのウイルス学体験講座」に班員を派遣し、アウトリーチ活動を行った。８．領域ニュースレターを発行した。

Current Status of Research Progress

1 :  Research has progressed more than it was originally planned.

Reason

総括班として、必須事項である総括班会議、第6回、第7回領域会議を滞りなく遂行した。また、共同研究インターンシップ、国際学会参加支援、若手研究会の開催を支援し、領域の若手研究者のサポートもできている。

Strategy for Future Research Activity

今後も本年度の方針を維持しつつ、最終年度に向かって領域終了後も次世代に繋がる方策を模索していく必要がある。特に、公募班とも連携し、領域内の交流を活性化して、共同研究インターンシップを推進する。また、ニュースレターの刊行や国内・国際学会を運営することで、研究領域の活性化と情報交換・発信に努める。

Research Products

• [Journal Article] Influenza Virus Induces Cholesterol-Enriched Endocytic Recycling Compartments for Budozone Formation via Cell Cycle-Independent Centrosome Maturation (2015)
  • Author(s): Kawaguchi A, Hirohama M, Harada Y, Osari S, Nagata K.
  • Journal Title: PLOS pathogens Volume : 11 Issue : 11 Pages : e1005284
  • Publisher: Public Library of Science
  • PMID: 26575487
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA (2015)
  • Author(s): Sugiyama K, Kawaguchi A, Okuwaki M, Nagata K.
  • Journal Title: Elife Volume : 4 Pages : e08939
  • Publisher: eLife Sciences Publications, Ltd
  • PMID: 26512887
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region (2015)
  • Author(s): Koga R, Sugita Y, Noda T, Yanagi Y, Ohno S.
  • Journal Title: Journal of Virology Volume : 89 Pages : 10524-10531
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide (2015)
  • Author(s): Kaneko M, Watashi K, Kamisuki S, Matsunaga H, Iwamoto M, Kawai F, Ohashi H, Tsukuda S, Shimura S, Suzuki R, Aizaki H, Sugiyama M, Park SY, Ito T, Ohtani N, Sugawara F, Tanaka Y, Mizokami M, Sureau C, Wakita T
  • Journal Title: J Virol Volume : 89 Pages : 11945-11953
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oseltamivir Expands Quasispecies of Influenza Virus through Cell-to-cell Transmission (2015)
  • Author(s): Mori K, Murano K, Ohniwa RL, Kawaguchi A, Nagata K.
  • Journal Title: Scientific reports Volume : 5 Pages : 9163
  • Publisher: Nature Publishing Group
  • PMID: 25772381
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Actin-myosin network is required for proper assembly of influenza virus particles (2015)
  • Author(s): Kumakura M, Kawaguchi A, Nagata K.
  • Journal Title: Virology Volume : 476 Pages : 141-150
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Artificial human Met agonists based on macrocycle scaffolds (2015)
  • Author(s): Ito K, Sakai K, Suzuki Y, Ozawa N, Hatta T, Natsume T, Matsumoto K, Suga H.
  • Journal Title: Nature Communications Volume : 6 Pages : 6373-6373
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity (2015)
  • Author(s): Fukushima, T., Yoshihara, H., Furuta, H., Kamei, H., Hakuno, F., Luan, J., Duan, C., Saeki, Y., Tanaka, K., Iemura, S., Natsume, T., Chida, K., Nakatsu, Y., Kamata, H., Asano, T., and Takabashi, S-I
  • Journal Title: Nature Communications Volume : 6 Pages : 6780-6780
  • Publisher: Nature Publishing Group
  • Year and Date: 2015-4-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP) (2014)
  • Author(s): Watashi K, Sluder A, Daito T, Matsunaga S, Ryo A, Nagamori S, Iwamoto M, Nakajima S, Tsukuda S, Borroto-Esoda K, Sugiyama M, Tanaka Y, Kanai Y, Kusuhara H, Mizokami M, Wakita T
  • Journal Title: Hepatology Volume : 59 Pages : 1726-1737
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection. (2014)
  • Author(s): Narita R, Takahasi K, Murakami E, Hirano E, Yamamoto SP, Yoneyama M, Kato H, Fujita T.
  • Journal Title: PLoS Pathog. Volume : 10 Pages : 1-11
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ZFP36L1 and ZFP36L2 control LDLR mRNA stability via the ERK-RSK pathway (2014)
  • Author(s): Adachi S, Homoto M, Tanaka R, Hioki Y, Murakami H, Suga H, Matsumoto M, Nakayama KI, Hatta T, Iemura S, Natsume T.
  • Journal Title: Nucleic Acids Research Volume : 42 Pages : 10037-10049
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli. (2014)
  • Author(s): Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, Kai C, Yada T, Suzuki Y, Yamada T, Ozawa T, Kaneki K, Inoue T, Kobayashi M, Kodama T, Wada Y, Sekimizu K, Akimitsu N.
  • Journal Title: Mol Cell. Volume : 53(3) Pages : 393-406
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of the N-terminal portion of influenza virus RNA polymerase subunit PB1 in nucleotide recognition (2014)
  • Author(s): Binh NT, Wakai C, Kawaguchi A, Nagata K.
  • Journal Title: Biochemical and biophysical research communications Volume : 443 Issue : 3 Pages : 975-979
  • Publisher: Elsevier Inc.
  • PMID: 24361882
  • Peer Reviewed
• [Journal Article] DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation. (2014)
  • Author(s): Yoo, J-S., Takahasi, K., Ng, CS., Ouda, R., Onomoto, K., Yoneyama, M., Lai, J-C., Lattmann, S., Nagamine, Y., Matsui, T., Iwabuchi, K., Kato, H. Fujita, T.
  • Journal Title: PLoS pathogens Volume : 10 Issue : 3 Pages : 1-18
  • Publisher: Public Library of Science
  • PMID: 24651521
  • Year and Date: 2014-3-20
  • Peer Reviewed / Open Access
• [Journal Article] The N-terminal region of influenza virus polymerase PB1 adjacent to the PA binding site is involved in replication but not transcription of the viral genome. (2013)
  • Author(s): Binh NT, Wakai C, Kawaguchi A, Nagata K.
  • Journal Title: Frontiers in Microbiology Volume : 4 Pages : 398-398
  • Peer Reviewed
• [Journal Article] DNA replication-dependent binding of CTCF plays a critical role in adenovirus genome functions (2013)
  • Author(s): Komatsu T, Sekiya T, Nagata K.
  • Journal Title: Scientific reports Volume : 3 Pages : 2187
  • Publisher: Nature Publishing Group
  • PMID: 23851926
  • Peer Reviewed
• [Journal Article] Signal peptidase complex subunit 1 participates in the assembly of hepatitis C virus through an interaction with E2 and NS2. (2013)
  • Author(s): Suzuki R, Matsuda M, Watashi K, Aizaki H, Matsuura Y, Wakita T, Suzuki T.
  • Journal Title: PLoS Pathogen Volume : 9(8) Pages : 1-12
  • Peer Reviewed
• [Journal Article] Signal peptidase complex subunit 1 participates in the assembly of hepatitis C virus through an interaction with E2 and NS2 (2013)
  • Author(s): Suzuki R, Matsuda M, Watashi K, Aizaki H, Matsuura Y, Wakita T, Suzuki T
  • Journal Title: PLoS Pathog Volume : 9 Pages : 1-12
  • Peer Reviewed
• [Journal Article] Specific inhibition of hepatitis C virus entry into host hepatocytes by fungi-derived sulochrin and its derivatives (2013)
  • Author(s): Nakajima S, Watashi K, Kamisuki S, Tsukuda S, Takemoto K, Matsuda M, Suzuki R, Aizaki H, Sugawara F, Wakita T
  • Journal Title: Biochem Biophys Res Commun Volume : 440(4) Pages : 515-20
  • Peer Reviewed
• [Journal Article] Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation after RNA virus infection. (2013)
  • Author(s): Ichinohe T, Yamazaki T, Koshiba T, Yanagi Y.
  • Journal Title: Proceeding National Academic Science USA Volume : 110(44) Pages : 17963-17968
  • Peer Reviewed
• [Journal Article] Transgenic mous model for the study of enterovirus 71 pathogenesis (2013)
  • Author(s): Fujii K, Nagata N, SatoY, Ong KC, Wong KT, Yamayoshi S, Shimanuki M, Shitara H, Taya C, Koike S
  • Journal Title: Proceedings of the National Academy of Science United States of America Volume : 110 Pages : 14753-14758
  • Peer Reviewed
• [Journal Article] Ero1-α and PDIs constitute a hierarchical electron transfer network of endoplasmic reticulum oxidoreductases. (2013)
  • Author(s): Araki K, Iemura S, Kamiya Y, Ron D, Kato K, Natsume T, Nagata K.
  • Journal Title: Journal of Cell Biology Volume : 202(6) Pages : 861-874
  • Peer Reviewed
• [Journal Article] Timing of the emergence of new successful viral strains in seasonal influenza. (2013)
  • Author(s): Omori R, Sasaki A.
  • Journal Title: Journal of Theoretical Biology Volume : 329 Pages : 32-38
  • Peer Reviewed
• [Presentation] Novel host factor-dependent influenza A virus vRNA synthesis from its cRNA. (2015)
  • Author(s): Sugiyama K, Kawaguchi A, Okuwaki M, Nagata K.
  • Organizer: The 14th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路夢舞台国際会議場（淡路）
  • Year and Date: 2015-9-9
  • Int'l Joint Research
• [Presentation] Intracellular trafficking of influenza virus genome mediated by endocytic recycling compartments located at the centrosome. (2015)
  • Author(s): Kawaguchi A, Hirohama M, Nagata K.
  • Organizer: The 16th International Negative Strand Virus Meeting
  • Place of Presentation: シエナ大学（シエナ）
  • Year and Date: 2015-6-15
  • Int'l Joint Research
• [Presentation] Influenza virus induces cholesterol-enriched endocytic recycling compartments for budozone formation through centrosome maturation. (2015)
  • Author(s): Kawaguchi A, Hirohama M, Nagata K.
  • Organizer: The 63rd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-23
  • Int'l Joint Research
• [Presentation] Multimerization of hepatitis B virus core protein regulated by microtubules (2015)
  • Author(s): Iwamoto M, Watashi K, Sugiyama M, Suzuki R, Aizaki H, Tanaka T, Mizokami M, Ohtani N, Koiwai O, Wakita T.
  • Organizer: The 63rd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-23
  • Int'l Joint Research
• [Presentation] RNA replicon as proper noun (2015)
  • Author(s): Nagata K.
  • Organizer: The 63rd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-22
  • Int'l Joint Research
• [Presentation] Development of a new animal model for enterovirus 71 infection (2015)
  • Author(s): Koike S.
  • Organizer: The 63rd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-22
  • Int'l Joint Research
• [Presentation] A novel function of human Pumilio proteins in innate immune responses (2015)
  • Author(s): Narita R, Yoneyama M, Kato H, Fujita T.
  • Organizer: The 63rd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-22
  • Int'l Joint Research
• [Presentation] Identification of a cellular protein contributing to the efficient growth of Murine gammaherpesvirus 68 (2015)
  • Author(s): Ohno S, Yanagi Y.
  • Organizer: The 63rd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-22
  • Int'l Joint Research
• [Presentation] 中心体の機能制御を介したインフルエンザウイルスゲノムの細胞内輸送機構 (2014)
  • Author(s): 川口敦史、広浜美香子、永田恭介
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Host factor-dependent influenza virus genome replication (2014)
  • Author(s): Nagata K.
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
  • Invited
• [Presentation] EV71の非神経組織での増殖はI型インターフェロンにより抑制されている (2014)
  • Author(s): 藤井健、小池智
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Ａｒｙｌ ｈｙｄｒｏｃａｒｂｏｎ ｒｅｃｅｐｔｏｒによる脂肪滴形成及びC型肝炎ウイルス粒子構築の制御 (2014)
  • Author(s): 大橋啓史、渡士幸一、中嶋翔、金ソルイ、鈴木亮介、相崎英樹、紙透伸治、菅原二三男、脇田隆字
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 麻疹ウイルス増殖におけるCofilinの機能 (2014)
  • Author(s): 古賀律子、大野真治、柳雄介
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Host factor-dependent RNA replication of the influenza virus genome. (2013)
  • Author(s): 永田恭介
  • Organizer: The 12th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: 淡路
  • Invited
• [Presentation] エンテロウイルス71受容体の解析 (2013)
  • Author(s): 小池智
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] C型肝炎ウイルス遺伝子型3aの培養細胞におけるウイルス感染実験系の確立 (2013)
  • Author(s): 金ソルイ、伊達朋子、横川寛、河野環、相崎英樹、脇田隆字
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 膜融合能が亢進した麻疹ウイルスはIFN betaを強く誘導する (2013)
  • Author(s): 渡辺俊平、白銀勇太、大野真治、柳雄介
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] PKR活性化制御を介するシクロフィリン阻害剤の新たな抗C型肝炎ウイルス作用機序 (2013)
  • Author(s): 大東卓史、渡士幸一、Ann Sluder、中嶋翔、Katyna Borroto-Esoda、藤田尚志、脇田隆字
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Remarks] ウイルス感染現象における宿主細胞コンピテンシーの分子基盤
• [Remarks] ウイルス感染現象における宿主細胞コンピテンシーの分子基盤
  • URL: http://www.md.tsukuba.ac.jp/basic-med/infcompetence/
• [Remarks] ウイルス感染現象における宿主細胞コンピテンシーの分子基盤
  • URL: http://www.md.tsukuba.ac.jp/basic-med/infcompetence/index.html
• [Funded Workshop] The 14th Awaji International Forum on Infection and Immunity (2015)
  • Place of Presentation: 淡路夢舞台国際会議場（淡路）
  • Year and Date: 2015-9-8