Host nuclear network responsible for the pathology of virus infection

• Project/Area Number: 26253083
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Akita University
• Principal Investigator: IMAI Yumiko 秋田大学, 医学(系)研究科(研究院), 教授 (50231163)
• Co-Investigator(Kenkyū-buntansha): 白髭 克彦 東京大学, 分子細胞生物学研究所, 教授 (90273854)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥41,730,000 (Direct Cost: ¥32,100,000、Indirect Cost: ¥9,630,000); Fiscal Year 2016: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000); Fiscal Year 2015: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000); Fiscal Year 2014: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
• Keywords: ウィルス / 集中治療 / エピゲノム / ウイルス / ゲノム / インフルエンザ / 染色体 / エピジェネティクス / 核内ネットワーク

Outline of Final Research Achievements

We investigated the mechanisms involved in the pathology of severe influenza virus infection focusing virus host nuclear interactions. We found a influenza virus RNA specific RNA nuclear export pathway mediated by NXF1. Also, we found that host epigenetic modifications in particular histone methylation play critical role in controlling the pathology of influenza virus infection, which could be a potential therapeutic target for severe influenza.

Research Products

• [Journal Article] ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage (2017)
  • Author(s): Sato T, Sato C, Kadowaki A, Watanabe H, Ho L, Ishida J, Yamaguchi T, Kimura A, Fukamizu A, Penninger JM, Reversade B, Ito H, Imai Y, Kuba K
  • Journal Title: Cardiovasc Res Volume: 113(7) Issue: 7 Pages: 760-769
  • DOI: 10.1093/cvr/cvx061
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy. (2017)
  • Author(s): Kimura H, Eguchi S, Sasaki J, Kuba K, Nakanishi H, Takasuga S, Yamazaki M, Goto A, Watanabe H, Itoh H, Imai Y, Suzuki A, Mizushima N, Sasaki T
  • Journal Title: JCI Insight Volume: 2 Issue: 1 Pages: 89462-89478
  • DOI: 10.1172/jci.insight.89462
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Evaluation of Lecithinized Superoxide Dismutase for the Prevention of Acute Respiratory Distress Syndrome in Animal Models (2017)
  • Author(s): Tanaka KI, Tamura F, Sugizaki T, Kawahara M, Kuba K, Imai Y, Mizushima T
  • Journal Title: Am J Respir Cell Mol Biol Volume: 56(2) Pages: 179-190
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Interaction of CCR4-NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis (2016)
  • Author(s): Yang CY, Ramamoorthy S, Boller S, Rosenbaum M, Rodriguez Gil A, Mittler G, Imai Y, Kuba K, Grosschedl R
  • Journal Title: Genes Dev Volume: 30(20) Pages: 2310-2324
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment (2016)
  • Author(s): Blank T, Detje CN, Spieß A, Hagemeyer N, Brendecke SM, Wolfart J, Staszewski O, Zöller T, Papageorgiou I, Schneider J, Paricio-Montesinos R, Eisel UL, Manahan-Vaughan D, Jansen S, Lienenklaus S, Lu B, Imai Y, Müller M, Goelz SE, Baker DP, Schwaninger M, Kann O, Heikenwalder M, Kalinke U, Prinz M
  • Journal Title: Immunity Volume: 44(4) Issue: 4 Pages: 901-12
  • DOI: 10.1016/j.immuni.2016.04.005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Potential cellular targets for anti-influenza drug development. (2016)
  • Author(s): Imai Y, Sakuma S, Imai H, Kuba K, Fujiwara S.
  • Journal Title: Cellular immunology and immunotherapies Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Virus-host interplay to influenza virus infection. (2016)
  • Author(s): Imai Y, Sakuma S, Imai H, Kuba K, Fujiwara S.
  • Journal Title: Joirnal of Pharmacoceutical Microbiology Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 脂肪酸代謝産物によるインフルエンザウイルス増殖抑制 (2016)
  • Author(s): 今井由美子
  • Journal Title: 感染・炎症・免疫 Volume: 印刷中
• [Journal Article] NTF2-like domain of Tap plays a critical role in cargo mRNA recognition and export. (2015)
  • Author(s): Katahira, J., Dimitrova, L., Imai, Y., Hurt, E.
  • Journal Title: Nucleic Acids Res. Volume: 43 Issue: 3 Pages: 1894-1904
  • DOI: 10.1093/nar/gkv039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of omega-3 PUFA-derived mediators, the protectins, in influenza virus (2015)
  • Author(s): Imai Y
  • Journal Title: Biochim Biophys Acta Volume: 1851 Issue: 4 Pages: 496-502
  • DOI: 10.1016/j.bbalip.2015.01.006
  • Peer Reviewed / Open Access
• [Journal Article] インフルエンザによる急性呼吸不全 (2015)
  • Author(s): 今井由美子
  • Journal Title: ER・ICUでの薬の使い方・考え方 ―エキスパートの実践と秘訣に学ぶ－2016-'17 ≪救急・集中治療 27 巻臨時増刊号≫ Volume: 4 Pages: 134-141
  • Peer Reviewed / Open Access
• [Journal Article] インフルエンザ感染におけるウイルス―宿主の核内相互作用 (2015)
  • Author(s): 今井由美子
  • Journal Title: 臨床免疫・アレルギー科 Volume: 64 Pages: 594-598
• [Presentation] 宿主核内相互作用を標的とした抗インフルエンザ薬の可能性 (2017)
  • Author(s): 今井由美子
  • Organizer: 日本薬学会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-26
  • Invited
• [Presentation] Dynamic changes in host chromatin architectures and histone modifications in response to influenza virus infection (2017)
  • Author(s): 今井由美子
  • Organizer: Epigenetics 2017 in RIKEN
  • Place of Presentation: 筑波
  • Year and Date: 2017-02-17
  • Int'l Joint Research / Invited
• [Presentation] 転写後制御を通したインフルエンザウイルス・宿主の核内相互作用 (2016)
  • Author(s): 今井由美子
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] ウイルスー宿主核内相互作用を標的としたウイルス感染症治療薬の可能性 (2016)
  • Author(s): 今井由美子
  • Organizer: 千里ライフサイエンスセミナー
  • Place of Presentation: 大阪
  • Year and Date: 2016-11-15
  • Invited
• [Presentation] インフルエンザウイルス感染に対する宿主核内応答機構 (2016)
  • Author(s): 今井由美子
  • Organizer: インターフェロン学会
  • Place of Presentation: 長崎
  • Year and Date: 2016-05-13
  • Invited
• [Presentation] 宿主核内相互作用を標的としたインフルエンザ治療薬の可能性 (2016)
  • Author(s): 今井由美子
  • Organizer: 感染症学会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-15
  • Invited
• [Presentation] 環境応答とエピジェネティクス：ウイルス感染に対する宿主エピゲノム応答機構 (2015)
  • Author(s): 今井由美子
  • Organizer: 日本分子生物学会・日本生化学会合同大会BMB2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-04
• [Presentation] 感染症治療薬、現状と今後の可能性 (2015)
  • Author(s): 今井由美子
  • Organizer: 日本学術会議東北地区後援会
  • Place of Presentation: 秋田
  • Year and Date: 2015-11-25
  • Invited
• [Presentation] Host-microbe interaction: Dynamic nuclear interaction between influenza virus and its host (2015)
  • Author(s): 今井由美子
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] Dynamic nuclear interactions between influenza virus and its host (2015)
  • Author(s): 今井由美子
  • Organizer: 感染症研究グローバルネットワークフォーラム2015
  • Place of Presentation: 千葉
  • Year and Date: 2015-11-14
  • Int'l Joint Research / Invited
• [Presentation] 宿主核内ネットワークを標的としたインフルエンザ治療薬の可能性 (2015)
  • Author(s): 今井由美子
  • Organizer: 新薬理学セミナー2015
  • Place of Presentation: 富山
  • Year and Date: 2015-09-19
  • Invited
• [Presentation] Potential of drug development targeting host signaling pathways (2015)
  • Author(s): 今井由美子
  • Organizer: 12th Congress of the World Federation of Society of Intensive and Critical Care Medicine
  • Place of Presentation: ソウル
  • Year and Date: 2015-09-01
  • Int'l Joint Research / Invited
• [Presentation] Potential of anti-influenza drug development targeting host nuclear network (2015)
  • Author(s): 今井由美子
  • Organizer: Wu Conference
  • Place of Presentation: 北京
  • Year and Date: 2015-08-12
  • Int'l Joint Research / Invited
• [Presentation] Influenza virus infection triggers histone modifications that link to viral pathogenicity (2015)
  • Author(s): Sakuma T, Higashiya M, Fujiwara S, Imai Y
  • Organizer: 日本薬理学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Dynamic nuclear interactions between influenza virus and its host (2015)
  • Author(s): Yumiko Imai
  • Organizer: IFRec symposium
  • Place of Presentation: 大阪
  • Year and Date: 2015-02-23 – 2015-02-24
  • Invited
• [Presentation] Influenza virus infection triggers histone modifications that link to viral pathogenicity (2015)
  • Author(s): Sakuma T, Higashiya M, Fujiwara S, Imai Y
  • Organizer: 4th Negative Strand Virus-Japan
  • Place of Presentation: 沖縄
  • Year and Date: 2015-01-19 – 2015-01-21
• [Presentation] インフルエンザウイルスの病原性発現を調節する核内ネットワーク (2014)
  • Author(s): 今井由美子
  • Organizer: 東北大学医学会講演会
  • Place of Presentation: 仙台
  • Year and Date: 2014-11-23
  • Invited
• [Presentation] Lipid metabolic pathways control the pathology of severe influenza virus infection (2014)
  • Author(s): Yumiko Imai
  • Organizer: The Awaji International Forum on Infection and Immunity
  • Place of Presentation: 神戸
  • Year and Date: 2014-09-24 – 2014-09-25
  • Invited
• [Presentation] ウイルス宿主相互作用からみたインフルエンザウイルスの病原性発現機構 (2014)
  • Author(s): 今井由美子
  • Organizer: 耳鼻咽喉科ニューロサイエンス研究会
  • Place of Presentation: 大阪
  • Year and Date: 2014-08-30
  • Invited
• [Presentation] 脂肪酸代謝物によるウイルスの病原性発現調節機構 (2014)
  • Author(s): 今井由美子
  • Organizer: 炎症学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-07-02 – 2014-07-04
  • Invited
• [Presentation] Lipid metabolic signals controls the pathology of influenza via RNA export machinery (2014)
  • Author(s): Yumiko Imai
  • Organizer: The Korean Society for Microbiology and Biotechnology
  • Place of Presentation: フサン
  • Year and Date: 2014-06-26 – 2014-06-27
  • Invited
• [Presentation] インフルエンザウイルス感染に対する宿主エピゲノム応答 (2014)
  • Author(s): 今井由美子
  • Organizer: エピジェネティクス研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-23 – 2014-05-24
  • Invited
• [Book] Frontiers in Anti-Infective Drug Discovery (2016)
  • Author(s): Yumiko Imai, Toshie Sakuma, Hirotaka Imai, Seiki Fujiwara, Keiji Kuba
  • Publisher: Bentham Science Publishers