Pathological study of severe influenza

• Project/Area Number: 26460447
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Nakajima Noriko 国立感染症研究所, 感染病理部, 室長 (60333358)
• 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: ¥1,560,000 (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: 重症インフルエンザ / インフルエンザ脳症 / ARDS / サイトカインストーム

Outline of Final Research Achievements

Although influenza is a self-limited disease, patients are complicated with acute respiratory distress syndrome (ARDS), encephalopathy, myocarditis symptoms and may die in some cases. Using pathological and molecular biological methods, we have examined autopsied tissues with influenza virus to find two pathological mechanisms of ARDS. One mechanism involves influenza virus clone that replicates well in alveolar epithelial cells. The patients develop viral pneumonia complicated with ARDS of pulmonary origin, which then leads to respiratory failure and the death of patients. The other mechanism involves infection-induced excessive immune responses. This then develops systemic inflammatory response syndrome (SIRS) concurrently with ARDS, and causes multiple organ failures. Furthermore, higher expression levels of inflammatory mediators were observed in brain tissues with influenza encephalopathy.

Research Products

• [Int'l Joint Research] National Hospital of Pediatrics(ベトナム)
• [Journal Article] Histopathological Findings of Lung with A/H1N1pdm09 Infection-Associated Acute Respiratory Distress Syndrome in the Post-Pandemic Season (2017)
  • Author(s): Hayashi K, Yoshida H, Sato Y, Tobiume M, Suzuki Y, Ariyoshi K, Hasegawa H, Nakajima N
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 70 Issue: 2 Pages: 197-200
  • DOI: 10.7883/yoken.JJID.2016.120
  • NAID: 130005475391
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Microminipig as an Animal Model for Influenza A Virus Infection (2016)
  • Author(s): Iwatsuki-Horimoto K, Nakajima N, Shibata M, Takahashi K, Sato Y, Kiso M, Yamayoshi S, Ito M, Enya S, Otake M, Kangawa A, da Silva Lopes TJ, Ito H, Hasegawa H, Kawaoka Y.
  • Journal Title: Journal of Virology Volume: 91 Issue: 2 Pages: 1-9
  • DOI: 10.1128/jvi.01716-16
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histopathologic findings of lung with A/H1N1pdm09 infection-associated ARDS in the post-pandemic season (2016)
  • Author(s): Hayashi K,Yoshida H, Sato Y, Tobiume M, Suzuki Y, Ariyoshi K, Hasegawa H, Nakajima N
  • Journal Title: Japanese Journal of Infectious Diseases Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Adenovirus Type 7 Pneumonia in Children Who Died from Measles-Associated Pneumonia, Hanoi, Vietnam, 2014 (2016)
  • Author(s): Hai le T, Thach HN, Tuan TA, Nam DH, Dien TM, Sato Y, Kumasaka T, Suzuki T, Hanaoka N, Fujimoto T, Katano H, Hasegawa H, Kawachi S, Nakajima N.
  • Journal Title: Emerging Infectious Diseases Volume: 22 Issue: 4 Pages: 687-690
  • DOI: 10.3201/eid2204.151595
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential. (2014)
  • Author(s): Watanabe T, Zhong G, Russell CA, Nakajima N, Hatta M, Hanson A, McBride R, Burke DF, Takahashi K, Fukuyama S, Tomita Y, Maher EA, Watanabe S, Imai M, Neumann G, Hasegawa H, Paulson JC, Smith DJ, Kawaoka Y
  • Journal Title: Cell Host and Microbe Volume: 15 Issue: 6 Pages: 692-705
  • DOI: 10.1016/j.chom.2014.05.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Severe lung injury associated with A/H1N1 pdm09 infection in the post-pandemic season. (2016)
  • Author(s): Noriko Nakajima, Akihiko Hamamatsu, Kino Hayashi, Yuko Sato, Toshio Kumasaka, Minoru Tobiume, Hideki Hasegawa
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] 近年のヒト分離H3N2インフルエンザウイルスに対するハムスターの感受性 (2016)
  • Author(s): 岩附 研子, 中島 典子, 長谷川 秀樹, 河岡 義裕
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 藤沢
  • Year and Date: 2016-09-06
• [Presentation] Post-mortem detection of adenovirus type 7 pneumonia in lungs of measles-associated pneumonia fatalities in a pediatric hospital, in Hanoi, Vietnam (2016)
  • Author(s): Noriko Nakajima
  • Organizer: US/Japan Cooperative Medical Science Program, 49th Joint Working Conference on Viral Diseases
  • Place of Presentation: Marriott North Bethesda, MD, USA
  • Year and Date: 2016-01-13
  • Int'l Joint Research
• [Presentation] Human Adenovirus Serptype-7-associated pneumonia in fatal cases of measles (2015)
  • Author(s): Noriko Nakajima, Hoang Ngoc Thach , Yuko Sato, Nozomu Hanaoka, Tsuguto Fujimoto, Tadaki Suzuki, Harutaka Katano, Le Thanh Hai、Hideki Hasegawa
  • 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] Pathological and molecular biological study of measles-associated pneumonia during measles outbreak in Vietnam in 2014 (2015)
  • Author(s): Noriko Nakajima
  • Organizer: Pediatric Conference 2015 of the National Hospital of Pediatrics
  • Place of Presentation: ハノイ、ベトナム
  • Year and Date: 2015-11-17
  • Int'l Joint Research / Invited
• [Presentation] Virological and histological study of 19 fatal cases of measles-associated pneumonia (2015)
  • Author(s): Noriko Nakajima, Yuko Sato, Toshio Kumasaka, Tsuguto Fujimoto, Nozomu Hanaoka, Tadaki Suzuki, Hideki Hasegawa
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] Modified In situ Hybridization AT-tailing to Visualize the Gene Expression in Formalin-Fixed and Paraffin-Embedded Tissues (2015)
  • Author(s): Noriko Nakajima, Yuko Sato, Osamu Kotani, Tadaki Suzuki, Toshiaki Kamei, Toru Takahashi, Tetsutaro Sata, Hideki Hasegawa
  • Organizer: USCAP 104 th Annual Meeting アメリカ・カナダ国際病理学会
  • Place of Presentation: Boston (アメリカ合衆国）
  • Year and Date: 2015-03-21 – 2015-03-28
• [Presentation] Correlations among Histopathological Characteristics, Viral distribution, and Cytokine/Chemokine Expression level within an Individual with A/H1N1pdm09 induced ARDS (2015)
  • Author(s): Kentaro Hayashi, Noriko Nakajima, Yuko Sato, Harutaka Katano, Noriyo Nagata, Tadaki Suzuki, Minoru Tobiume, Hiroshi Yoshida, Yoshio Suzuki, Toshio Kumasaka, Tetsutaro Sata, Kota Ariyoshi, Hideki Hasegawa
  • Organizer: USCAP 104 th Annual Meeting アメリカ・カナダ国際病理学会
  • Place of Presentation: Boston (アメリカ合衆国）
  • Year and Date: 2015-03-21 – 2015-03-28
• [Presentation] スペイン風邪ウイルスに類似の鳥インフルエンザウイルスのパンデミックポテンシャル (2014)
  • Author(s): 渡辺登喜子 Gongxun Zhong Colin Russell 中島典子 八田正人 Anthony Handson 高橋健太 渡辺真治 今井正樹 長谷川秀樹 河岡義裕
  • 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] ヒトから分離されたH7N9亜型鳥インフルエンザウイルス感染動物モデルの病理学的解析 (2014)
  • Author(s): 中島典子、渡辺登喜子、佐藤由子、高橋健太、鈴木忠樹、田代眞人、河岡義裕、長谷川秀樹
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26