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フラビウイルスの共生と進化に関与する宿主及びウイルス因子の解析

Planned

Project AreaNeo-virology: the raison d'etre of viruses
Project/Area Number 16H06432
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka University

Principal Investigator

松浦 善治  大阪大学, 微生物病研究所, 教授 (50157252)

Co-Investigator(Kenkyū-buntansha) 吉住 朋晴  九州大学, 医学研究院, 准教授 (80363373)
Project Period (FY) 2016-06-30 – 2021-03-31
Project Status Granted (Fiscal Year 2020)
Budget Amount *help
¥117,520,000 (Direct Cost: ¥90,400,000、Indirect Cost: ¥27,120,000)
Fiscal Year 2020: ¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2019: ¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2018: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
Fiscal Year 2017: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
Fiscal Year 2016: ¥29,770,000 (Direct Cost: ¥22,900,000、Indirect Cost: ¥6,870,000)
Keywords共進化 / 分泌性糖蛋白質 / 粒子形成 / GC含量 / フラビウイルス科ウイルス / 膜結合性蛋白質 / ウイルス進化 / フラビウイルス / 進化 / NS1 / アポリポ蛋白質 / ペギウイルス / 共生 / ウイルス粒子産生 / ウイルス
Outline of Annual Research Achievements

現在、フラビウイルス科ウイルスの進化機構として、(1)フラビウイルス科ウイルスの粒子産生に関わる宿主由来のアポリポ蛋白質とウイルス由来のErnsまたはNS1蛋白質の共通性に関する研究を行なっている。また、新たな持続感染機構の解明として(2)ペギウイルス感染機構の解明に関する研究を行なっている。
1)C型肝炎ウイルス(HCV)及びペスチウイルスの粒子形成において宿主由来のアポリポ蛋白質とウイルス由来のNS1及びErnsが共通した機能を持つことを明らかにし、報告した(PLoS Pathogens 2017)。さらに、分泌蛋白質の機能解析を進めるツールとして様々なフラビウイルス科ウイルスにスプリットnLucレポーターを搭載したウイルス(HCV、ペスチウイルス、デングウイルス、日本脳炎ウイルス)を作出し、報告した(J Viriol 2018)。さらに、最近NS1の機能を欠損したフラビウイルスの作出に成功し、現在ウイルス複製またはウイルス粒子形成に関与するNS1の変異体としてI273Eを同定した。このNS1変異体はウイルスゲノムの複製は起きるものの、ウイルス粒子産生は認められないことから、NS1が粒子形成にも重要な役割を持つことが明らかになった。
2)九州大学との共同研究によってペギウイルス陽性の臨床検体の収集を開始した。これまでに、肝臓移植後の患者ではペギウイルス陽性率が健常人と比べて明らかに高いことが明らかになった。また、ペギウイルス陽性末梢血単核球では非感染と比較してISGの発現が誘導されていることがRNA-seq解析から明らかになった。このことから、持続感染しているペギウイルスも症状は認めないものの、免疫応答に少なくとも影響を与えている可能性が示唆された。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

フラビウイルス科ウイルスの進化に関する研究に関しては、2017年と2018年に論文報告できており、現在も投稿準備中であることからも分かる通り、予定通りにおおむね順調に進展していると考えられる。ペギウイルス研究も新規知見が得られ、論文投稿準備中であり、順調に経過していると考えられる。

Strategy for Future Research Activity

フラビウイルスの進化における分泌蛋白質の役割の保存性を検討する。特に、フラビウイルスの粒子形成におけるNS1の役割を宿主由来のアポリポ蛋白質や他のウイルス由来のErnsが代替できるかを検討する。
また、ペギウイルスは持続感染していることが明らかになっているが、その免疫回避機構を明らかにする予定である。

Report

(3 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report

Research Products

(40 results)

All 2018 2017 2016 Other

All Journal Article Presentation Book Remarks

  • [Journal Article] Induction of selective autophagy in cells replicating hepatitis C virus genome.2018

    • Author(s)
      Mori Hiroyuki、Fukuhara Takasuke、Ono Chikako、Tamura Tomokazu、Sato Asuka、Fauzyah Yuzy、Wada Masami、Okamoto Toru、Noda Takeshi、Yoshimori Tamotsu、Matsuura Yoshiharu
    • Journal Title

      J. Gen. Virol.

      Volume: 99 Pages: 1643-1657

    • DOI

      10.1099/jgv.0.001161

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Infection with flaviviruses requires BCLXL for cell survival2018

    • Author(s)
      Suzuki T, Okamoto T, Katoh H, Sugiyama Y, Kusakabe S, Tokunaga M, Hirano J, Miyata Y, Fukuhara T, Ikawa M, Satoh T, Yoshio S, Suzuki R, Saijo M, Huang DCS, Kanto T, Akira S Matsuura Y
    • Journal Title

      PLOS Pathogens

      Volume: 14

    • DOI

      10.1371/journal.ppat.1007299

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of recombinant Flaviviridae viruses possessing a small reporter tag.2018

    • Author(s)
      Tamura T, Fukuhara T, Uchida T, Ono C, Mori H, Sato A, Fauzyah Y, Okamoto T, Kurosu T, Setoh YX, Imamura M, Tautz N6 Sakoda Y, Khromykh AA, Chayama K, Matsuura Y.
    • Journal Title

      J Virol

      Volume: 92 Pages: 1-19

    • DOI

      10.1128/jvi.01582-17

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of SPP inhibitors suppressing propagation of HCV and protozoa.2017

    • Author(s)
      Hirano J, Okamoto T, Sugiyama Y, Suzuki T, Kusakabe S, Tokunaga M, Fukuhara T, Sasai M, Tougan T, Matsunaga Y, Yamashita K, Sakai Y, Yamamoto M, Horii T, Standley DM, Moriishi K, Moriya K, Koike K, Matsuura Y.
    • Journal Title

      PNAS

      Volume: 114

    • DOI

      10.1073/pnas.1712484114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of Apoptosis during Flavivirus Infection2017

    • Author(s)
      Okamoto T, Suzuki T, Kusakabe S, Tokunaga M, Hirano J, Miyata Y, Matsuura Y
    • Journal Title

      Viruses

      Volume: 9 Pages: 243-243

    • DOI

      10.3390/v9090243

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae.2017

    • Author(s)
      Fukuhara Takasuke、Tamura Tomokazu、Ono Chikako、Shiokawa Mai、Mori Hiroyuki、Uemura Kentaro、Yamamoto Satomi、Kurihara Takeshi、Okamoto Toru、Suzuki Ryosuke、Yoshii Kentaro、Kurosu Takeshi、Igarashi Manabu、Aoki Hiroshi、Sakoda Yoshihiro、Matsuura Yoshiharu
    • Journal Title

      PLoS Pathog

      Volume: 13

    • DOI

      10.1371/journal.ppat.1006475

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of miR-122-independent propagation of HCV2017

    • Author(s)
      C. Ono, T. Fukuhara, D. Motooka, S. Nakamura, D. Okuzaki, S. Yamamoto, T. Tamura, H. Mori, A. Sato, K. Uemura, Y. Fauzyah, T. Kurihara, T. Suda, A. Nishio, Su Su Hmwe, T. Okamoto, T. Tatsumi, T. Takehara, K. Chayama, T. Wakita, K. Koike, Y. Matsuura
    • Journal Title

      PLOS Pathogens

      Volume: -

    • DOI

      10.1371/journal.ppat.1006374

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity2017

    • Author(s)
      Fukuhara T, Yamamoto S, Ono C, Nakamura S, Motooka D, Mori H, Kurihara T, Sato A, Tamura T, Motomura T, Okamoto T, Imamura M, Ikegami T, Yoshizumi T, Soejima Y, Maehara Y, Chayama K, Matsuura Y.
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: 7 Pages: 1-10

    • DOI

      10.1038/srep45228

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CD14+ monocyte-derived galectin-9 induces natural killer cell cytotoxicity in chronic hepatitis C2017

    • Author(s)
      Nishio A, Tatsumi T, Nawa T, Suda T, Yoshioka T, Onishi Y, Aono S, Shigekawa M, Hikita H, Sakamori R, Okuzaki D, Fukuhara T, Matsuura Y, Hiramatsu N, Takehara T
    • Journal Title

      Hepatology

      Volume: 65 Pages: 18-31

    • DOI

      10.1002/hep.28847

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human Cathelicidin Compensates for the Role of Apolipoproteins in Hepatitis C Virus Infectious Particle Formation.2016

    • Author(s)
      Puig-Basagoiti F., Fukuhara T., Tamura T., Ono C., Uemura K., Kawachi Y., Yamamoto S., Mori H., Kurihara T., Okamoto T., Aizaki H., Matsuura Y.
    • Journal Title

      Journal of Virology

      Volume: 90 Pages: 1-14

    • DOI

      10.1128/jvi.00471-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] TRC8-dependent degradation of the immature core protein regulates propagation and pathogenesis of hepatitis C virus2016

    • Author(s)
      Aizawa S., Okamoto T., Sugiyama Y., Kouwaki T., Ito A., Suzuki T., Ono C., Fukuhara T., Yamamoto M., Okochi M., Hiraga N., Imamura M., Chayama K., Suzuki R., Shoji I., Moriishi K., Moriya K., Koike K., and Matsuura Y.
    • Journal Title

      Nature Communications

      Volume: 7 Pages: 1-12

    • DOI

      10.1038/ncomms11379

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Lipoprotein receptors redundantly participate in entry of hepatitis C virus2016

    • Author(s)
      Yamamoto S., Fukuhara T., Ono C., Uemura K., Kawachi Y., Shiokawa M., Mori H., Wada M., Shima R., Okamoto T., Hiraga N., Suzuki R., Chayama K., Wakita T., Matsuura Y.
    • Journal Title

      PLoS Pathogens

      Volume: 12 Pages: 1-24

    • DOI

      10.1371/journal.ppat.1005610

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] フラビウイルス科ウイルスの病原性と宿主特異性に関する研究2018

    • Author(s)
      田村友和
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] In vivo propagation of recombinant Flaviviridae viruses possessing NanoLuc subunit2018

    • Author(s)
      Tomokazu Tamura, Takasuke Fukuhara, Manabu Igarashi, Takuro Uchida, Bazarragchaa Enkhbold, Chikako Ono, Hiroyuki Mori, Asuka Sato, Yuzy Fauzyah, Toru Okamoto, Yoshihiro Sakoda, Kazuaki Chayama, Yoshiharu Matsuura
    • Organizer
      The 37th American Society of Virology 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] In vivo propagation of recombinant Flaviviridae viruses possessing NanoLuc subunit2018

    • Author(s)
      Tomokazu Tamura1, Takasuke Fukuhara1, Manabu Igarashi2, Takuro Uchida3, Bazarragchaa Enkhbold4, Chikako Ono1, Hiroyuki Mori1, Asuka Sato1, Yuzy Fauzyah1, Toru Okamoto1, Yoshihiro Sakoda4, Kazuaki Chayama,3 and Yoshiharu Matsuura1
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] フラビウイルスの粒子産生機構の解析2017

    • Author(s)
      福原 崇介
    • Organizer
      平成28年度北海道大学遺伝子病制御研究所「感染、免疫、がん、炎症」研究集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] フラビウイルス科ウイルスの粒子形成におけるウイルスまたは宿主因子の関与2017

    • Author(s)
      福原 崇介
    • Organizer
      第14回ウイルス学キャンプin湯河原
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規レポーター遺伝子を搭載したフラビウイルス科ウイルスの作出とその応用2017

    • Author(s)
      田村 友和
    • Organizer
      第14回ウイルス学キャンプin湯河原
    • Related Report
      2017 Annual Research Report
  • [Presentation] Viral secretory proteins Erns and NS1 play comparable roles with apolipoproteins in the infectious particle formation of Flaviviridae2017

    • Author(s)
      福原 崇介
    • Organizer
      The American Society for Virology (ASV) the 36th Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characterization of Flaviviridae viruses possessing a reporter gene2017

    • Author(s)
      田村 友和
    • Organizer
      The American Society for Virology (ASV) the 36th Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Engineering of small reporter-tagged Flaviviridae viruses applicable to antiviral screening and in vivo dynamics2017

    • Author(s)
      田村 友和
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Engineering of Small Reporter-Tagged Flaviviridae Viruses Applicable to Antiviral Screening and in vivo Dynamics2017

    • Author(s)
      田村 友和
    • Organizer
      24th International Symposium on Heepatitis C Virus and Related Viruses
    • Related Report
      2017 Annual Research Report
  • [Presentation] Viral secretory glycoproteins of Pestivirus and Flavivirus have similar roles with exchangeable apolipoproteins on the formation of infectious HCV particles2017

    • Author(s)
      福原 崇介
    • Organizer
      24th International Symposium on Heepatitis C Virus and Related Viruses
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characterization of recombinant Flaviviridae viruses possessing a small reporter-tag2017

    • Author(s)
      田村 友和
    • Organizer
      第16回あわじしま感染症・免疫フォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Viral secretory glycoproteins Erns and NS1 play comparable roles with apolipoproteins in infectious particle formation of Flaviviridae2017

    • Author(s)
      福原 崇介
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] C型肝炎ウイルスの増殖と病原性に関与する宿主因子2017

    • Author(s)
      松浦善治、福原崇介、岡本 徹
    • Organizer
      第2回北大部局横断シンポジウム「免疫・癌・感染」
    • Place of Presentation
      札幌
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Viral secretory glycoproteins of Flaviviridae virus have similar roles with apolipoproteins on the formation of infectious HCV particles2016

    • Author(s)
      Takasuke Fukuhara, Tomokazu Tamura , Mai Shiokawa , Chikako Ono , Satomi Yamamoto , Hiroyuki Mori , Takeshi Kurihara , Kentaro Uemura , Toru Okamoto , Hiroshi Aoki , Yoshihiro Sakoda , Yoshiharu Matsuura
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] G28A mutation facilitates an efficient propagation of HCV in miR-122-independent manner2016

    • Author(s)
      Chikako Ono, Takasuke Fukuhara, Daisuke Motooka, Shota Nakamura, Satomi Yamamoto, Hiroyuki Mori, Kentaro Uemura, Toru Okamoto, Su Su Hmwe, Kazuaki Chayama, Takaji Wakita, Kazuhiko Koike, and Yoshiharu Matsuura
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] The roles of secretory glycoproteins in viral particle formation in family Flaviviridae2016

    • Author(s)
      Tomokazu Tamura, Takasuke Fukuhara, Mai Shiokawa, Chikako Ono, Satomi Yamamoto, Hiroyuki Mori, Takeshi Kurihara, Toru Okamoto, Hiroshi Aoki, Yoshihiro Sakoda and Yoshiharu Matsuura
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Regulation of Bcl-2 family proteins in cells infected with Flaviviruses2016

    • Author(s)
      Tatsuya Suzuki, Toru Okamoto, Takasuke Fukuhara,Yoshiharu Matusuura
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Signal peptide peptidase participates in propagation and pathogenesis of hepatitis C virus2016

    • Author(s)
      Yoshiharu Matsuura, Toru Okamoto
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Non-canonical LC3 lipidation induced by HCV inhibits autophagic flux2016

    • Author(s)
      Hiroyuki Mori, Takasuke Fukuhara, Chikako Ono, Tomokazu Tamura, Satomi Yamamoto, Kentaro Uemura, Toru Okamoto1, Masami Wada, Takeshi Noda, Tamotsu Yoshimori, Yoshiharu Matsuura
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hepatitis C virus core protein interacts with Bnip3 and soppresses its dimerizatin and binding with LC32016

    • Author(s)
      Takeya Tsusumi,Akari Kado,Kazuya Okushin,Kenichiro Enooku,Hidetaka Fiujinaga,Kyoji Moriya,Hiroshi Yotsuyanagi,Yumi Kanegae,Izumu Sauto,Yoshiharu Mtsuura,Kazuhiko Koike
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human hepatic stellate cells are permissive for hepatitis C virus infection/replication and play important role in fibrosis2016

    • Author(s)
      Takuma Zaitsu,Haruyo Aoyagi,Mami Matsuda,Noriyuki Watanabe,Akira Fujimoto,Koichi Watashi,Ryosuke Suzuki,Takasuke Fukuhara,Yoshiharu Matsuura,Kenjiro Wake,Tetsuro Suzuki,Tomokazu,Matsuura,Koji Tamura,Takaji Wakita,Hideki Aizaki
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Annexins participate in thte HCV RNA replication2016

    • Author(s)
      Tkakayuki Abe,Ikuo Shoji,Yoshiharu Matsuura
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human BDCA3+DCs utilize-λfor inducing intrahepatic anti-viral ISGs and stimulating bystander Immune cells in HCV Infection2016

    • Author(s)
      Sachiyo Yoshio,Masaya Sugiyama,Takasuke Fukuhara,Yoshiharu Matsuura,Masashi Mizokami,Tatsuta Kanto.
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Single peptide peptidase a target for anti-HCV drug2016

    • Author(s)
      Toru Okamoto,Junki Hirano,Tatsuya Suzuki, ,Shinji Kusakabe,Takasuke Fukuhara Kohji Moriishi,Kazuhiko Koike and Yoshiharu Matsuura
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of Bcl-2 family proteins in cells infected with Flaviviruses2016

    • Author(s)
      Toru Okamoto,Tatsuya Suzuki, ,Shinji Kusakabe,Junki Hirano,Makoto Tokunaga, Takasuke Fukuhara and Yoshiharu Matsuura
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      京都
    • Year and Date
      2016-10-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Book] Hepatitis C Virus I2016

    • Author(s)
      Kohji Moriichi and Yoshiharu Matsuura
    • Total Pages
      362
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Remarks] 大阪大学微生物病研究所分子ウイルス分野

    • URL

      http://www-yoshi.biken.osaka-u.ac.jp

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-07-04   Modified: 2020-08-26  

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