The role of exosomes released from Epstein-Barr virus-infected cells

• Project/Area Number: 26460545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: Nanbo Asuka 北海道大学, 医学研究院, 准教授 (60359487)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Epstein-Barrウイルス / エキソソーム / miRNA / 次世代シーケンシング / microRNA

Outline of Final Research Achievements

Infection of Epstein-Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative and EBV-infected B cells by next-generation sequencing. We found that the biogenesis of exosomes is upregulated in EBV-infected cells compared with EBV-negative cells. We also observed that viral and several specific host microRNAs were predominantly incorporated in the exosomes released from EBV-infected cells. Our findings indicate that EBV infection modulates the biogenesis of exosomes and the profile of exosomal microRNAs, potentially contributing to phenotypic changes in cells receiving these exosomes.

Research Products

• [Int'l Joint Research] ウィスコンシン大学マディソン校(米国)
• [Int'l Joint Research] ウィスコンシン大学マディソン校/マッカードル癌研究所(米国)
• [Int'l Joint Research] University of Wisconsin, Madison(米国)
• [Journal Article] Ebola virus requires a host scramblase for externalization of phosphatidylserine on the surface of viral particles (2018)
  • Author(s): Nanbo Asuka、Maruyama Junki、Imai Masaki、Ujie Michiko、Fujioka Yoichiro、Nishide Shinya、Takada Ayato、Ohba Yusuke、Kawaoka Yoshihiro
  • Journal Title: PLoS Pathog Volume: 14 Issue: 1 Pages: e1006848-e1006848
  • DOI: 10.1371/journal.ppat.1006848
  • NAID: 120006416019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epstein-Barr Virus Acquires Its Final Envelope on Intracellular Compartments With Golgi Markers (2018)
  • Author(s): Nanbo Asuka、Noda Takeshi、Ohba Yusuke
  • Journal Title: Front Microbiol Volume: 9 Pages: 454-454
  • DOI: 10.3389/fmicb.2018.00454
  • NAID: 120006416029
  • Peer Reviewed / Open Access
• [Journal Article] Inside the Cell: Assembly of Filoviruses (2017)
  • Author(s): Kolesnikova Larissa、Nanbo Asuka、Becker Stephan、Kawaoka Yoshihiro
  • Journal Title: Curr Top Microbiol Immunol Volume: 411 Pages: 353-380
  • DOI: 10.1007/82_2017_15
  • ISBN: 9783319689463, 9783319689487
  • Int'l Joint Research
• [Journal Article] Improved FRET Biosensor for the Measurement of BCR-ABL Activity in Chronic Myeloid Leukemia Cells (2017)
  • Author(s): M. Horiguchi, M. Fujioka, T. Kondo, Y. Fujioka, X. Li, K. Horiuchi, A.O. Satoh, P. Nepal, S. Nishide, A. Nanbo, T. Teshima and Y. Ohba.
  • Journal Title: Cell Structure and Function Volume: 42 Issue: 1 Pages: 15-26
  • DOI: 10.1247/csf.16019
  • NAID: 130005308488
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access
• [Journal Article] Epstein-Barr virus exploits host endocytic machinery for cell-to-cell viral transmission rather than a virological synapse. (2016)
  • Author(s): A. Nanbo, K. Kachi, H. Yoshiyama and Y. Ohba.
  • Journal Title: J. Gen. Virol. Volume: 97 Issue: 11 Pages: 2989-3006
  • DOI: 10.1099/jgv.0.000605
  • NAID: 120006360051
  • Peer Reviewed / Open Access
• [Journal Article] Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection. (2016)
  • Author(s): Furuyama W, Marzi A, Carmody AB, Maruyama J, Kuroda M, Miyamoto H, Nanbo A, Manzoor R, Yoshida R, Igarashi M, Feldmann H, Takada A.
  • Journal Title: PLoS Pathog. Volume: 12(12)
  • NAID: 120005981447
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Discovery of an antibody for pan-ebolavirus therapy (2016)
  • Author(s): Furuyama D, Marzi A, Nanbo A, Haddock E, Maruyama J, Miyamoto H, Igarashi M, Yoshida R, Dr. Noyori O, Feldmann H, Takada A
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 20514-20514
  • DOI: 10.1038/srep20514
  • NAID: 120005906783
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C (2016)
  • Author(s): Inuzuka T, Fujioka Y, Tsuda M, Fujioka M, Satoh AO, Horiuchi K, Nishide S, Nanbo A, Tanaka S, Ohba Y
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 21613-21613
  • DOI: 10.1038/srep21613
  • NAID: 120005722549
  • Peer Reviewed / Open Access
• [Journal Article] Receptor activator of NF-κB ligand induces cell adhesion and integrin α2 expression via NF-κB in head and neck cancers (2016)
  • Author(s): T.Yamada, M. Tsuda, T. Wagatsuma, Y. Fujioka, M. Fujioka, A. O. Satoh, K. Horiuchi, S. Nishide, A. Nanbo, Y. Totsuka, H. Haga, S. Tanaka, M. Shindoh, and Y. Ohba
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 23545-23545
  • DOI: 10.1038/srep23545
  • NAID: 120005753715
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Interaction between TIM-1 and NPC1 is important for the cellular entry of Ebola virus (2015)
  • Author(s): Kuroda M, Fujikura D, Nanbo A, Marzi A, Noyori O, Kajihara M, Maruyama J, Matsuno K, Miyamoto H, Yoshida R, Feldmann H, Takada A
  • Journal Title: J. Virol. Volume: 印刷中 Issue: 12 Pages: 6481-6493
  • DOI: 10.1128/jvi.03156-14
  • NAID: 120005621883
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comprehensive high-throughput RNA sequencing analysis reveals contamination of multiple nasopharyngeal carcinoma cell lines with HeLa cell genomes. (2014)
  • Author(s): Strong MJ, Baddoo M, Nanbo A, Xu M, Puetter A, Lin Z.
  • Journal Title: J Virol. Volume: 88 Issue: 18 Pages: 10696-10704
  • DOI: 10.1128/jvi.01457-14
  • Peer Reviewed
• [Presentation] エボラウイルスエンベロープへのホスファチジルセリン集積に関与する宿主スクランブラーゼの同定 (2018)
  • Author(s): 南保明日香
  • Organizer: 7th Negative Strand Virus-Japan (サザンビーチホテル＆リゾート沖縄, 糸満市)
• [Presentation] Epstein-Barrウイルス粒子出芽機構に関する研究 (2017)
  • Author(s): 南保明日香，Bill Sugden，大場雄介
  • Organizer: 第31回ヘルペスウイルス研究会 (松江ニューアーバンホテル、松江市）
• [Presentation] 細胞接触を介したEpstein-Barrウイルス感染機構における分子機構の解明 (2017)
  • Author(s): 南保明日香，加持邦弘，吉山裕規，大場雄介
  • Organizer: 第14回EBV研究会 (旭川グランドホテル、旭川市）
• [Presentation] EBOV requires a host scramblase for its efficient entry (2017)
  • Author(s): Nanbo A，Maruyama J，Komatsu H，Watanabe T，Fujimuro M，Takada A，Ohba Y，Kawaoka Y
  • Organizer: 第65回日本ウイルス学会学術集会（大阪国際会議場、大阪市）
• [Presentation] EBOV requires a host scramblase for its efficient entry (2017)
  • Author(s): Nanbo A, Maruyama J，Watanabe T，Fujimuro M，Ohba Y，Takada A，Kawaoka Y
  • Organizer: 9th International Symposium on Filoviruses (Welcome Hotel Marburg, Marburg)
  • Int'l Joint Research
• [Presentation] エボラウイルス侵入におけるエンベロープリン脂質の役割 (2016)
  • Author(s): 南保明日香
  • Organizer: 5th Negative Strand Virus-Japan
  • Place of Presentation: ホテルモントレ沖縄(恩納村）
  • Year and Date: 2016-01-26
• [Presentation] Epstein-Barr virus exploits host endocytic machinery for cell-to-cell viral transmission (2016)
  • Author(s): Nanbo A, Kachi K, Yoshiyama H, Ohba Y
  • Organizer: 17th International symposium on Epstein-Barr virus and associated disease
  • Place of Presentation: University of Tower, Zurich, Switzerland
  • Int'l Joint Research
• [Presentation] Characterization of exosomes derived from Epstein-Barr virus-infected cells (2016)
  • Author(s): Nanbo A, Katano H, Iizasa H, Yoshiyama H, Sugden B, Ohba Y
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター, 札幌
• [Presentation] Trafficking of adhesion molecules via recycling endosomes is crucial for cell-to-cell contact-mediated Epstein-Barr virus transmission (2015)
  • Author(s): Asuka Nanbo, Hironori Yoshiyama, Yusuke Ohba
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡市）
  • Year and Date: 2015-11-22
• [Presentation] Characterization of exosomes derived from Epstein-Barr virus-infected cells (2015)
  • Author(s): Asuka Nanbo, Harutaka Katano, Hironori Yoshiyama
  • Organizer: EBウイルス研究会
  • Place of Presentation: ビッグハート出雲(出雲市)
  • Year and Date: 2015-07-21
  • Int'l Joint Research
• [Presentation] Bio-imaging of entry process of Ebolavirus (2015)
  • Author(s): Asuka Nanbo
  • Organizer: 17th International Conference on Emerging Infectious Diseases (EID)
  • Place of Presentation: Academia Sinica (Taipei, Taiwan)
  • Year and Date: 2015-01-25
  • Invited
• [Presentation] ウイルス感染の分子機構～ウイルスと宿主間相互作用～ (2015)
  • Author(s): 南保明日香
  • Organizer: 第10回九大・北大合同活動報告会
  • Place of Presentation: 都市センタービル（東京）
  • Year and Date: 2015-01-15
  • Invited
• [Presentation] 細胞間接触を介した上皮細胞へのEBV伝播の分子機構に関する研究 (2014)
  • Author(s): 南保明日香、吉山裕規、大場雄介
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜会議センター(横浜市)
  • Year and Date: 2014-11-10
• [Presentation] フィロウイルスの細胞侵入におけるTIM-1とNPC1相互作用の解析 (2014)
  • Author(s): 黒田誠、藤倉大輔、南保明日香、野依修、梶原将大、丸山隼輝、宮本洋子、吉田玲子、高田礼人
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜会議センター(横浜市)
  • Year and Date: 2014-11-10
• [Presentation] ウイルス-宿主相互作用を可視化する (2014)
  • Author(s): 南保明日香
  • Organizer: 第87回日本生化学会大会シンポジウム
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-10-15
  • Invited
• [Presentation] Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveolae-dependent endocytosis and promote phenotypic modulation in the target cells (2014)
  • Author(s): Nanbo A, Kawanishi E, Yoshida R, Yoshiyama H
  • Organizer: 2014 ASEMV Annual Meeting
  • Place of Presentation: Asilomar Conference Center (Monterrey, USA)
  • Year and Date: 2014-10-11
• [Presentation] Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveolae-dependent endocytosis and promote phenotypic modulation in the target cells (2014)
  • Author(s): Nanbo A, Kawanishi E, Yoshida R, Yoshiyama H
  • Organizer: 39th Annual International Herpesvirus Workshop
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2014-07-20
• [Presentation] 細胞間接触を介した上皮細胞へのEBV伝播の分子機構に関する研究 (2014)
  • Author(s): 南保明日香、吉山裕規、大場雄介
  • Organizer: 第11回EBウイルス研究会
  • Place of Presentation: 国立感染症研究所（東京）
  • Year and Date: 2014-06-27
• [Book] Marburg and Ebola Viruses: From Ecosystems to Molecules, Inside the Cell (2017)
  • Author(s): Kolesnikova L, Nanbo A, Kawaoka Y, and Becker S,
  • Publisher: Springer
• [Book] EBウイルス関連胃癌 (2017)
  • Author(s): 南保明日香
  • Publisher: 診断と治療社
• [Book] Marburg and Ebola Viruses: From Ecosystems to Molecules, Inside the Cell (2016)
  • Author(s): Kolesnikova L, Nanbo A, Kawaoka Y, and Becker S
  • Publisher: Springer
• [Book] EBウイルス関連胃癌 (2016)
  • Author(s): 南保明日香
  • Publisher: 診断と治療社
• [Book] EBウイルス (2015)
  • Author(s): 南保明日香
  • Total Pages: 10
  • Publisher: 診断と治療社
• [Patent(Industrial Property Rights)] フィロウイルス感染阻害剤のスクリーニング法 (2014)
  • Inventor(s): 高田礼人, 南保明日香, 黒田誠, 藤倉大輔
  • Industrial Property Rights Holder: 高田礼人, 南保明日香, 黒田誠, 藤倉大輔
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-210419
  • Filing Date: 2014-10-15