Infectious mechanism of avian influenza viruses based on cellular endosomal pH

• Project/Area Number: 15K09576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Daidoji Tomo 京都府立医科大学, 医学(系)研究科(研究院), 講師 (80432433)
• Co-Investigator(Kenkyū-buntansha): 渡邊 洋平 京都府立医科大学, 医学(系)研究科(研究院), 講師 (50452462)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 鳥インフルエンザウイルス

Outline of Final Research Achievements

The purpose of this study was to clarify the mechanism of avian influenza viruses to infect human airway epithelial cells, from aspects of both the virus genome and host cells. Viral infectivity in human airway epithelial cell clones was different between currently circulating avian influenza virus isolated from humans and the virus from birds. This distinct infectivity was determined by the specific amino acid sequences, located in individual genomes of the viruses from human and birds. Next, we assessed the infectivity of avian influenza viruses in differentiated human airway epithelial cell clones. The difference in viral infectivity in differentiated human airway epithelial cell clones may be associated with the difference in cell differentiation.

Research Products

• [Journal Article] Development of a new ex vivo model for evaluation of endoscopic submucosal injection materials performance (2018)
  • Author(s): Hirose Ryohei、Nakaya Takaaki、Naito Yuji、Daidoji Tomo、Yasuda Hiroaki、Konishi Hideyuki、Itoh Yoshito
  • Journal Title: J Mech Behav Biomed Mater. Volume: 79 Pages: 219-225
  • DOI: 10.1016/j.jmbbm.2018.01.002
  • Peer Reviewed
• [Journal Article] Characterization of H5N1 influenza virus quasispecies with adaptive hemagglutinin mutations from single-virus infections of human airway cells (2018)
  • Author(s): 1.Watanabe Y**, Arai Y, Kawashita N, Ibrahim MS, Elgendy EM, Daidoji T, Kajikawa J, Hiramatsu H, Sriwilaijaroen N, Ono T, Takagi T, Takahashi K, Shioda T, Matsumoto K, Suzuki Y, Nakaya T
  • Journal Title: J Virol. Volume: 印刷中 Issue: 11
  • DOI: 10.1128/jvi.02004-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces: Mucus Protects Virions From Acid and Digestive Juices. (2017)
  • Author(s): Hirose R, Nakaya T**, Naito Y, Daidoji T, Watanabe Y, Yasuda H, Konishi H, Itoh Y.
  • Journal Title: J Infect Dis. Volume: 216 Issue: 1 Pages: 105-109
  • DOI: 10.1093/infdis/jix224
  • Peer Reviewed / Open Access
• [Journal Article] Unique Infectious Strategy of H5N1 Avian Influenza Virus Is Governed by the Acid-Destabilized Property of Hemagglutinin. (2017)
  • Author(s): Daidoji T**, Watanabe Y, Arai Y, Kajikawa J, Hirose R, Nakaya T
  • Journal Title: Viral Immunol. Volume: 30 Issue: 6 Pages: 398-407
  • DOI: 10.1089/vim.2017.0020
  • Peer Reviewed / Open Access
• [Journal Article] Viscosity is an important factor of resistance to alcohol-based disinfectants by pathogens present in mucus. (2017)
  • Author(s): Hirose R, Nakaya T**, Naito Y, Daidoji T, Watanabe Y, Yasuda H, Konishi H, Itoh Y.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 13186-13186
  • DOI: 10.1038/s41598-017-13732-2
  • Peer Reviewed / Open Access
• [Journal Article] Long term detection of seasonal influenza RNA in faeces and intestine - Author's Reply (2017)
  • Author(s): Hirose R, Nakaya T, Daidoji T
  • Journal Title: Clin Microbiol Infect Volume: 23 Issue: 4 Pages: 273-274
  • DOI: 10.1016/j.cmi.2016.09.020
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of polymerase gene mutations that affect viral replication in H5N1 influenza viruses isolated from pigeons. (2017)
  • Author(s): Elgendy EM, Arai Y, Kawashita N, Daidoji T, Takagi T, Ibrahim MS, Nakaya T, Watanabe Y
  • Journal Title: J Gen Virol. Volume: 98 Issue: 1 Pages: 6-17
  • DOI: 10.1099/jgv.0.000674
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Long-term detection of seasonal influenza RNA in faeces and intestine. (2016)
  • Author(s): Hirose R, Daidoji T, Naito Y, Watanabe Y, Arai Y, Oda T, Konishi H, Yamawaki M, Itoh Y, Nakaya T.
  • Journal Title: Clin Microbiol Infect Volume: 22 Issue: 9 Pages: 813-813
  • DOI: 10.1016/j.cmi.2016.06.015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Genetic characterization of highly pathogenic avian influenza H5N1 viruses isolated from naturally infected pigeons in Egypt (2016)
  • Author(s): Elgendy EM, Watanabe Y, Daidoji T, Arai Y, Ikuta K, Ibrahim MS, Nakaya T
  • Journal Title: Virus Genes Volume: 52 Issue: 6 Pages: 867-871
  • DOI: 10.1007/s11262-016-1369-z
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses (2016)
  • Author(s): Arai Y, Kawashita N, Daidoji T, Ibrahim MS, El-Gendy EM, Takagi T, Takahashi K, Suzuki Y, Ikuta K, Nakaya T, Shioda T, Watanabe Y
  • Journal Title: PLoS Pathog. Volume: 12 Issue: 4 Pages: e1005583-e1005583
  • DOI: 10.1371/journal.ppat.1005583
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Influenza A Virus-Induced Expression of a GalNAc Transferase, GALNT3, via MicroRNAs Is Required for Enhanced Viral Replication. (2015)
  • Author(s): Nakamura S, Horie M, Daidoji T, Honda T, Yasugi M, Kuno A, Komori T, Okuzaki D, Narimatsu H, Nakaya T, Tomonaga K.
  • Journal Title: J Virol. Volume: 90 Issue: 4 Pages: 1788-801
  • DOI: 10.1128/jvi.02246-15
  • Peer Reviewed / Open Access
• [Journal Article] H5N1鳥インフルエンザウイルスHAの宿主適応機構 (2015)
  • Author(s): 渡邊 洋平、大道寺 智、中屋 隆明
  • Journal Title: ウイルス Volume: 65 Pages: 187-198
  • NAID: 130005431375
• [Presentation] 分化条件下における鳥インフルエンザウイルスのヒト呼吸器上皮由来細胞株への感染様式について (2018)
  • Author(s): 大道寺 智
  • Organizer: 7th Negative Strand Virus-Japan Symposium
• [Presentation] 鳥インフルエンザウイルス感染の分子メカニズムについて (2018)
  • Author(s): 大道寺 智
  • Organizer: 戦略的研究基盤形成事業成果報告シンポジウム
  • Invited
• [Presentation] Avian influenza virus infection in human airway epithelial cell model (2017)
  • Author(s): Tomo Daidoji, Junichi Kajikawa, Yohei Watanabe, Yasuha Arai, Ryohei Hirose, Takaaki Nakaya
  • Organizer: JSPS Core-to-Core Program, 2nd Scientific Seminar
• [Presentation] Mechanism of Seasonal Influenza Virus Persistence in Human Digestive Tract: Mucus Protects Virions From Acid and Digestive Juices (2017)
  • Author(s): Takaaki Nakaya, Ryohei Hirose, Tomo Daidoji, Yuji Naito, Yohei Watanabe, Yasuha Arai, Kaho Kawada, Jun-Ichi Kajikawa, Masanaga Yamawaki, Yoshito Itoh
  • Organizer: 第６５回日本ウイルス学会学術集会
• [Presentation] Evaluation of avian influenza virus infection in differentiated airway epithelial cells (2017)
  • Author(s): Tomo Daidoji, Masafumi Noguchi, Junichi Kajikawa, Yohei Watanabe, Yasuha Arai, Ryohei Hirose, Mitsuru Morimoto, Takaaki Nakaya
  • Organizer: 第６５回日本ウイルス学会学術集会
• [Presentation] Novel polymerase gene mutations for human adaptation in clinical isolates of Avian H5N1 influenza virus in Asia (2017)
  • Author(s): Yasuha Arai, Norihito Kawashita, Kozue Hotta, Mai Phuong Vu Hoang, Khanh Hang Le Nguyen, Thach Co Nguyen, Cuong Duc Vuong, Mai Quynh Le, Kosuke Soda, Junichi Kajikawa, Tomo Daidoji, Takaaki Nakaya, Tatsuya Takagi, Toshihiro Ito, Futoshi Hasebe, Tatsuo Shioda, Yohei Watanabe
  • Organizer: 第６５回日本ウイルス学会学術集会
• [Presentation] Characterization of H5N1 influenza virus with HA mutations diversified in human airway epithelial cells as minor variants (2017)
  • Author(s): Yohei Watanabe, Yasuha Arai, Norihito Kawashita, Tomo Daidoji, Emad M Elgendy, Madiha S Ibrahim, Junichi Kajikawa, Hiroaki Hiramatsu, Tatsuya Takagi, Kazuo Takahash, Tatsuo Shioda, Yasuo Suzuki, Takaaki Nakaya
  • Organizer: 第６５回日本ウイルス学会学術集会
• [Presentation] "Hemagglutinin acid stability and viral infection in H7 influenza virus" "H7インフルエンザウイルスHA蛋白質のpH感受性と感染性について" (2016)
  • Author(s): Tomo Daidoji, Emad M. Elgendy, Yohei Watanabe, Yasuha Arai, Madiha S. Ibrahim, Kazuyoshi Ikuta, Takaaki Nakaya
  • 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
  • Year and Date: 2016-10-23
• [Presentation] "Characterization of H5N1 influenza virus variants with HA mutations selected during the viral replication in human airway epithelial cells " "H5N1鳥インフルエンザウイルスがヒト呼吸器上皮細胞での複製過程で獲得するHA変異の特性" (2016)
  • Author(s): Yohei Watanabe, Yasuha Arai, Tomo Daidoji, Emad Elgendy, Madiha Ibrahim, Kazuo Takahashi, Tatsuo Shioda, Kazuyoshi Ikuta, Yasuo Suzuki, Takaaki Nakaya
  • 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
  • Year and Date: 2016-10-23
• [Presentation] "Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses" "H5N1高病原性鳥インフルエンザウイルスポリメラーゼ遺伝子におけるヒト適応変異の同定" (2016)
  • Author(s): Yasuha Arai, Norihito Kawashita, Tomo Daidoji, Madiha Ibrahim, Kazuo Takahashi,Yasuo Suzuki, Takaaki Nakaya, Tatsuo Shioda, Kazuyoshi Ikuta, Yohei Watanabe
  • 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
  • Year and Date: 2016-10-23
• [Presentation] "Identification of unique mutations that influence the polymerase activity of H5N1 avian influenza virus isolated from pigeons" "ハト由来H5N1鳥インフルエンザウイルスの特徴的なポリメラーゼ活性に影響する変異の同定" (2016)
  • Author(s): Emad Elgendy, Yasuha Arai, Madiha Ibrahim, Tomo Daidoji, Kazuyoshi Ikuta,Takaaki Nakaya, Yohei Watanabe
  • 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
  • Year and Date: 2016-10-23
• [Presentation] H7鳥インフルエンザウイルスにおけるHA蛋白質のpH感受性について (2016)
  • Author(s): 大道寺 智
  • Organizer: 5th Negative Strand Virus-Japan Symposium
  • Place of Presentation: ホテルモントレ
  • Year and Date: 2016-01-26
• [Presentation] "Identification of human adaptive mutations in the polymerase complex of H5N1 avian influenza virus in Egypt" "H5N1鳥インフルエンザウイルスポリメラーゼ複合体における新規ヒト適応性変異の同定" (2015)
  • Author(s): Yasuha Arai，Tomo Daidoji，Madiha Ibrahim，Kazuo Takahashi，Yasuo Suzuk， Takaaki Nakaya，Tatsuo Sioda，Kazuyoshi Ikuta，Yohei Watanabe
  • 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
  • Year and Date: 2015-11-23
• [Presentation] "Dynamics of influenza A virus infection in mucin-type glycosyltransferase Galnt3-knockout mice" "ムチン型糖転移酵素 Galnt3ノックアウトマウスを用いた A 型インフルエンザウイルス感染動態の解析" (2015)
  • Author(s): Shoko Nakamura，Tomo Daidoji，Tomoyuki Honda，Takaaki Nakaya，Toshihisa Komori，Keizo Tomonaga
  • 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
  • Year and Date: 2015-11-23
• [Presentation] "Genetic diversification of H5N1 avian influenza virus variants during replication in human airway epithelial cells" "H5N1鳥インフルエンザウイルスがヒト呼吸器上皮細胞での複製過程で獲得する遺伝子多様性" (2015)
  • Author(s): Yohei Watanabe，Yasuha Arai，Tomo Daidoji，Ibrahim Madiha，Elgendy Emad，Kazuo Takahashi，Yasuo Suzuki，Tatsuo Sioda，Kazuyoshi Ikuta，Takaaki Nakaya
  • 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
  • Year and Date: 2015-11-23
• [Presentation] "Hemagglutinin acid stability in H7 influenza virus infection of host cells" "H7鳥インフルエンザウイルス感染における HA 蛋白質の pH 安定性について" (2015)
  • Author(s): Tomo Daidoji，Elgendy Emad M，Watanabe Yohei，Ibrahim Madiha S，Kazuyoshi Ikuta，Takaaki Nakaya
  • 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
  • Year and Date: 2015-11-22
• [Presentation] Genetic characterization of H5N1 avian influenza virus from pigeon in Egypt 2009 (2015)
  • Author(s): Elgendy Emad，Ibrahim Madiha S.，Yasuha Arai，Tomo Daidoji，Yohei, Watanabe，Takaaki Nakaya
  • 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
  • Year and Date: 2015-11-22