Detection of antiviral-resistant influenza viruses

• Project/Area Number: 26460816
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Takashita Emi 国立感染症研究所, インフルエンザウイルス研究センター, 主任研究官 (30361249)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 抗インフルエンザ薬 / 薬剤性ウイルス / 薬剤耐性ウイルス

Outline of Final Research Achievements

The surveillance of antiviral-resistant viruses is important for public health authorities and clinicians to control influenza. Here, we improved fluorescence-based and chemiluminescence-based neuraminidase (NA) inhibition assays for determining influenza susceptibility to NA inhibitors, oseltamivir, zanamivir, peramivir and laninamivir. Then we established a cell-based screening system to evaluate the susceptibility of influenza viruses to a novel antiviral drug, favipiravir, a viral RNA-dependent RNA polymerase inhibitor.

Research Products

• [Journal Article] Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015. (2016)
  • Author(s): Hurt AC, Besselaar TG, Daniels RS, Ermetal B, Fry A, Gubareva L, Huang W, Lackenby A, Lee RT, Lo J, Maurer-Stroh S, Nguyen HT, Pereyaslov D, Rebelo-de-Andrade H, Siqueira MM, Takashita E, Tashiro M, Tilmanis D, Wang D, Zhang W, Meijer A.
  • Journal Title: Antiviral Res. Volume: 132 Pages: 178-185
  • DOI: 10.1016/j.antiviral.2016.06.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir. (2016)
  • Author(s): Takashita E, Ejima M, Ogawa R, Fujisaki S, Neumann G, Furuta Y, Kawaoka Y, Tashiro M, Odagiri T.
  • Journal Title: Antiviral Res. Volume: 132 Pages: 170-177
  • DOI: 10.1016/j.antiviral.2016.06.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Influenza A(H1N1)pdm09 virus exhibiting enhanced cross-resistance to oseltamivir and peramivir due to a dual H275Y/G147R substitution, Japan, March 2016. (2016)
  • Author(s): Takashita E, Fujisaki S, Shirakura M, Nakamura K, Kishida N, Kuwahara T, Shimazu Y, Shimomura T, Watanabe S, Odagiri T; Influenza Virus Surveillance Group of Japan.
  • Journal Title: Euro Surveill. Volume: 21 Issue: 24 Pages: 30258-30258
  • DOI: 10.2807/1560-7917.es.2016.21.24.30258
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus. (2016)
  • Author(s): Sakai K, Ami Y, Nakajima N, Nakajima K, Kitazawa M, Anraku M, Takayama I, Sangsriratanakul N, Komura M, Sato Y, Asanuma H, Takashita E, Komase K, Takehara K, Tashiro M, Hasegawa H, Odagiri T, Takeda M.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 29430-29430
  • DOI: 10.1038/srep29430
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of an A (H1N1)pdm09 Virus Imported from India in March 2015 (2016)
  • Author(s): Takashita E, Fujisaki S, Shirakura M, Nakamura K, Kishida N, Kuwahara T, Ohmiya S, Sato K, Ito H, Chiba F, Nishimura H, Shindo S, Watanabe S, Odagiri T; Influenza Virus Surveillance Group of Japan.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 69 Issue: 1 Pages: 83-86
  • DOI: 10.7883/yoken.JJID.2015.460
  • NAID: 130005120243
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 6SLN-lipo PGA specifically catches (coats) human influenza virus and synergizes neuraminidase-targeting drugs for human influenza therapeutic potential. (2015)
  • Author(s): Sriwilaijaroen N, Suzuki K, Takashita E, Hiramatsu H, Kanie O, Suzuki Y.
  • Journal Title: J Antimicrob Chemother. Volume: 70 Issue: 10 Pages: 2797-80
  • DOI: 10.1093/jac/dkv193
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] C646, a Novel p300/CREB-Binding Protein-Specific Inhibitor of Histone Acetyltransferase, Attenuates Influenza A Virus Infection. (2015)
  • Author(s): Zhao D, Fukuyama S, Sakai-Tagawa Y, Takashita E, Shoemaker JE, Kawaoka Y.
  • Journal Title: Antimicrob Agents Chemother. Volume: 60 Issue: 3 Pages: 1902-6
  • DOI: 10.1128/aac.02055-15
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 4th isirv-AVG Conference Novel Antiviral Therapies for Influenza and other Respiratory参加報告 (2015)
  • Author(s): 高下恵美
  • Journal Title: インフルエンザ Volume: 56 Pages: 228-9
• [Journal Article] Characterization of a Large Cluster of Influenza A(H1N1)pdm09 Viruses Cross-Resistant to Oseltamivir and Peramivir during the 2013-2014 Influenza Season in Japan. (2015)
  • Author(s): Takashita E, Kiso M, Fujisaki S, Yokoyama M, Nakamura K, Shirakura M, Sato H, Odagiri T, Kawaoka Y, Tashiro M.
  • Journal Title: Antimicrob Agents Chemother. Volume: 59 Issue: 5 Pages: 2607-2617
  • DOI: 10.1128/aac.04836-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2013-2014. (2015)
  • Author(s): Takashita E, Meijer A, Lackenby A, Gubareva L, Rebelo-de-Andrade H, Besselaar T, Fry A, Gregory V, Leang SK, Huang W, Lo J, Pereyaslov D, Siqueira MM, Wang D, Mak GC, Zhang W, Daniels RS, Hurt AC, Tashiro M.
  • Journal Title: Antiviral Res. Volume: 117 Pages: 27-38
  • DOI: 10.1016/j.antiviral.2015.02.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 抗インフルエンザ薬と薬剤耐性ウイルス (2015)
  • Author(s): 高下恵美、河岡義裕、田村大輔
  • Journal Title: インフルエンザ Volume: 16 Pages: 7-13
• [Journal Article] タミフル・ラピアクタ耐性インフルエンザウイルス (2015)
  • Author(s): 高下恵美
  • Journal Title: 医学のあゆみ Volume: 252 Pages: 312-313
• [Journal Article] Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012-2013. (2014)
  • Author(s): Meijer A, Rebelo-de-Andrade H, Correia V, Besselaar T, Drager-Dayal R, Fry A, Gregory V, Gubareva L, Kageyama T, Lackenby A, Lo J, Odagiri T, Pereyaslov D, Siqueira MM, Takashita E, Tashiro M, Wang D, Wong S, Zhang W, Daniels RS, Hurt AC.
  • Journal Title: Antiviral Res. Volume: 110 Pages: 31-41
  • DOI: 10.1016/j.antiviral.2014.07.001
  • Peer Reviewed / Open Access
• [Journal Article] 抗インフルエンザ薬耐性A(H1N1)pdm09インフルエンザの流行 (2014)
  • Author(s): 高下恵美
  • Journal Title: 感染・炎症・免疫 Volume: 44 Pages: 75-76
• [Journal Article] 各都道府県の抗インフルエンザ薬耐性ウイルス調査はどのように行われているのでしょうか (2014)
  • Author(s): 高下恵美
  • Journal Title: インフルエンザ Volume: 15 Pages: 22-22
• [Journal Article] 耐性インフルエンザウイルスの動向 (2014)
  • Author(s): 高下恵美
  • Journal Title: 臨床と研究 Volume: 91 Pages: 45-48
• [Presentation] 日本国内で検出されたA(H1N1)pdm09二重耐性変異ウイルスの性状解析. (2017)
  • Author(s): 高下恵美.
  • Organizer: 6th Negative Strand Virus-Japan
  • Place of Presentation: 沖縄
  • Year and Date: 2017-01-16
• [Presentation] 2015/16シーズンに検出されたオセルタミビル・ペラミビルに強い耐性を示すインフルエンザウイルス. (2016)
  • Author(s): 高下恵美, 小川理恵, 藤崎誠一郎, 白倉雅之, 三浦秀佳, 中村一哉, 岸田典子, 桑原朋子, 菅原裕美, 佐藤彩, 秋元未来, 渡邉真治, 小田切孝人.
  • Organizer: 第48回日本小児感染症学会
  • Place of Presentation: 岡山
  • Year and Date: 2016-11-19
• [Presentation] Detection of influenza A(H1N1)pdm09 viruses exhibiting enhanced cross-resistance to oseltamivir and peramivir in the 2015/16 season. (2016)
  • Author(s): Takashita E, Fujisaki S, Shirakura M, Nakamura K, Kishida N, Kuwahara T, Shimazu Y, Shimomura T, Doi I, Watanabe S, Odagiri T, The Influenza Virus Surveillance Group of Japan.
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] Antiviral susceptibility of influenza viruses isolated from patients pre-and post-administration of favipiravir. (2016)
  • Author(s): Takashita E, Ejima M, Ogawa R, Fujisaki S, Neumann G, Furuta Y, Kawaoka Y, Tashiro M, Odagiri T.
  • Organizer: Options IX for the Control of Influenza
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2016-08-24
  • Int'l Joint Research
• [Presentation] 日本国内におけるNA阻害薬耐性インフルエンザウイルス検出状況 (2016)
  • Author(s): 高下恵美
  • Organizer: 5th Negative Strand Virus-Japan
  • Place of Presentation: ホテルモントレ沖縄 (沖縄県国頭郡)
  • Year and Date: 2016-01-25
• [Presentation] Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir (2015)
  • Author(s): Takashita E, Fujisaki S, Neumann G, Furuta Y, Kawaoka Y, Tashino M, Odagiri T.
  • Organizer: 第63回日本ウイルス学会
  • Place of Presentation: 福岡国際会議場 (福岡県福岡市)
  • Year and Date: 2015-11-22
• [Presentation] 2014/15シーズンにおける日本国内の抗インフルエンザ薬耐性ウイルス検出状況 (2015)
  • Author(s): 高下恵美、小川理恵、藤崎誠一郎、中村一哉、白倉雅之、岸田典子、桑原朋子、菅原裕美、佐藤彩、三浦秀佳、秋元未来、渡邉真治、小田切孝人
  • Organizer: 第47回日本小児感染症学会
  • Place of Presentation: ザ・セレクトン福島、ホテル福島グリーンパレス、コラッセふくしま (福島県福島市)
  • Year and Date: 2015-10-31
• [Presentation] Characterization of a Large Cluster of Influenza A(H1N1)pdm09 Virus Cross-Resistant to Oseltamivir and Peramivir during the 2013-2014 Influenza Season in Japan (2015)
  • Author(s): Takashita E, Kiso M, Fujisaki S, Yokohama M, Nakamura K, Shirakura M, Sato H, Odagiri T, Kawaoka Y, Tashino M.
  • Organizer: 4th ISIRV-AVG Conference
  • Place of Presentation: University of Texas at Austin (Texas, USA)
  • Year and Date: 2015-06-02
  • Int'l Joint Research
• [Presentation] オセルタミビル・ペラミビル耐性A(H1N1)pdm09インフルエンザウイルスの地域流行 (2015)
  • Author(s): 高下恵美
  • Organizer: 4th Negative Strand Virus-Japan
  • Place of Presentation: ラグナガーデンホテル（沖縄県宜野湾市）
  • Year and Date: 2015-01-19 – 2015-01-21
• [Presentation] 2013/14シーズンにおけるNA阻害剤耐性A(H1N1)pdm09ウイルスの地域流行 (2014)
  • Author(s): 高下恵美、江島美穂、藤崎誠一郎、横山勝、中村一哉、白倉雅之、菅原裕美、佐藤彩、佐藤裕徳、小田切孝人、全国地方衛生研究所
  • Organizer: 第62回日本ウイルス学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 2013/14シーズンにおける抗インフルエンザ薬耐性ウイルスの地域流行と高度耐性ウイルスの検出について (2014)
  • Author(s): 高下恵美、江島美穂、藤崎誠一郎、中村一哉、白倉雅之、菅原裕美、佐藤彩、小田切孝人
  • Organizer: 第46回日本小児感染症学会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November 2013 to February 2014 (2014)
  • Author(s): E Takashita, M Ejima, S Fujisaki, M Yokoyama, K Nakamura, M Shirakura, H Sugawara, A Sato, H Sato, M Tashiro, T Odagiri
  • Organizer: 5th ESWI Influenza Conference
  • Place of Presentation: Radisson Blu Hotel Latvija (Riga, Latvia)
  • Year and Date: 2014-09-14 – 2014-09-17
• [Presentation] 札幌市を中心とした抗インフルエンザ薬耐性ウイルスの地域流行 (2014)
  • Author(s): 高下恵美、江島美穂、藤崎誠一郎、中村一哉、 白倉雅之、菅原裕美、佐藤 彩、小田切孝人
  • Organizer: 第28回インフルエンザ研究者交流の会シンポジウム
  • Place of Presentation: 鳥取市総合福祉センター（鳥取県鳥取市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan (2014)
  • Author(s): E Takashita, M Ejima, S Fujisaki, K Nakamura, A Sato, H Sugawara, M Tashiro and T Odagiri
  • Organizer: 3rd isirv-AVG Conference; Influenza and other Respiratory Virus Infections: Advances in Clinical Management
  • Place of Presentation: Keio Plaza Hotel (Tokyo, Japan)
  • Year and Date: 2014-06-04 – 2014-06-06
• [Book] インフルエンザ診療ガイド2016-17 (2016)
  • Author(s): 高下恵美.
  • Total Pages: 4
  • Publisher: 日本医事新報社
• [Book] インフルエンザ診療ガイド2015-16 (2015)
  • Author(s): 高下恵美
  • Total Pages: 4
  • Publisher: 日本医事新報社
• [Book] インフルエンザ診療ガイド2014-15 (2014)
  • Author(s): 高下恵美
  • Total Pages: 4
  • Publisher: 日本医事新報社
• [Remarks] 抗インフルエンザ薬耐性株サーベイランス
  • URL: http://www.nih.go.jp/niid/ja/influ-resist.html