Molecular mechanism of centrosome activation regulated by influenza virus infection

• Project/Area Number: 26860299
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: University of Tsukuba
• Principal Investigator: Kawaguchi Atsushi 筑波大学, 医学医療系, 助教 (90532060)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: インフルエンザウイルス / 中心体 / YB-1 / 核膜 / 微小管 / インフルエンザ

Outline of Final Research Achievements

YB-1 accumulates in the centrosome with influenza virus genome and formed a toroidal structure with a beads-on-a-string distribution around centriole. We also found that YB-1 localized at the centrosome in uninfected cells during mitotic phase and stimulates microtubule nucleation from the centrosome. Thus, it is likely that influenza virus recruits YB-1 at the centrosome to stimulate microtubule assembly. It is also revealed that, in infected cells, recycling endosomes accumulate in pericentrosomal organelle, called endocytic recycling compartments (ERC), through the centrosome maturation by recruiting YB-1. Further, we found that cholesterol accumulates in ERC with the virus genome and the cholesterol-enriched ERC is important for clustering of viral membrane proteins at the plasma membrane. These results suggest that cholesterol could be a trigger for budozone formation concomitantly with the virus genome trafficking to the plasma membrane (PLoS Pathog., 2015).

Research Products

• [Journal Article] The RNA- and TRIM25-Binding Domains of Influenza Virus NS1 Protein Are Essential for Suppression of NLRP3 Inflammasome-Mediated Interleukin-1β Secretion (2016)
  • Author(s): Moriyama, M. et al.
  • Journal Title: J. Virol. Volume: 90 Issue: 8 Pages: 4105-4114
  • DOI: 10.1128/jvi.00120-16
  • Peer Reviewed / Int'l Joint Research
• [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-e1005284
  • DOI: 10.1371/journal.ppat.1005284
  • NAID: 120007129744
  • 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
  • DOI: 10.7554/elife.08939
  • NAID: 120007135522
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Centrosome maturation requires YB-1 to regulate dynamic instability of microtubules for nucleus reassembly. (2015)
  • Author(s): Kawaguchi A, Asaka MN, Matsumoto K, Nagata K.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 8768-8768
  • DOI: 10.1038/srep08768
  • NAID: 120007130347
  • Peer Reviewed / Open Access / 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 Issue: 1 Pages: 9163-9163
  • DOI: 10.1038/srep09163
  • NAID: 120007130320
  • 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
  • DOI: 10.1016/j.virol.2014.12.016
  • Peer Reviewed / 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 and Akimitsu N.
  • Journal Title: Molecular cell Volume: 53 Issue: 3 Pages: 393-406
  • DOI: 10.1016/j.molcel.2014.01.009
  • Peer Reviewed / Open Access
• [Presentation] Intracellular trafficking of influenza virus genome via centrosome maturation. (2015)
  • Author(s): Kawaguchi A.
  • Organizer: The 38th Annual meeting of the Molecular Biology Society for Japan
  • Place of Presentation: 神戸国際会議場（神戸）
  • Year and Date: 2015-12-04
  • Invited
• [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] 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: 2015-09-09
  • 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: 2015-06-15
  • 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] インフルエンザウイルスポリメラーゼサブユニット間の適合性 (2014)
  • Author(s): 原田芳美、永田恭介、川口敦史
  • 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] インフルエンザウイルス粒子形成におけるアクトミオシンネットワークの機能 (2014)
  • Author(s): 熊倉充子、川口敦史、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] インフルエンザウイルスcell-to-cell感染によるウイルスゲノムの多様化 (2014)
  • Author(s): 森幸太郎、川口敦史、村野健作、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] 宿主因子によって制御されるインフルエンザウイルスゲノムの細胞内動態 (2014)
  • Author(s): 川口敦史
  • Organizer: 第11回ウイルス学キャンプin湯河原
  • Place of Presentation: 熱海
  • Year and Date: 2014-09-17
  • Invited
• [Remarks] 筑波大学 分子ウイルス学分野
  • URL: http://www.md.tsukuba.ac.jp/basic-med/infectionbiology/virology/