Elucidation of factors that cause the biennial epidemic of influenza C virus and factors that make infected children more severe

• Project/Area Number: 18K07783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Yamagata University
• Principal Investigator: Matsuzaki Yoko 山形大学, 医学部, 准教授 (00292417)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: インフルエンザ / 呼吸器感染症 / 抗原変異

Outline of Final Research Achievements

The cause of the biennial epidemic of influenza C virus was investigated from the antigenic variation on the virus side and the immunity on the host side. The amino acid substitution K190N of the surface protein found in the 2018 isolates was in the neutralizing epitope, suggesting that the epidemic may have spread due to antigen variation. The antibody survey against influenza C virus detected several cases of increased antibody titers in adults before the epidemic in children, indicating that reinfection in immunized adults helped select epidemic strains and affected the epidemic in children.

Academic Significance and Societal Importance of the Research Achievements

C型インフルエンザの小児での流行に、ウイルスの抗原変異と成人の再感染が関係することを明らかにできた。この成果を他の呼吸器ウイルスの解析に応用することが期待できる。大きな流行になれば小児の重症化例も増える。中和エピトープの場所を同定したことと、本研究でその場所の変異による増殖への影響をみたことにより、今後のサーベイランスで得られる自然分離株の遺伝子変異を抗原変異と結び付けることが可能になり、流行拡大への影響を推測することが出来るようになった。

Research Products

• [Journal Article] Isolation of Human Coronaviruses OC43, HKU1, NL63, and 229E in Yamagata, Japan, Using Primary Human Airway Epithelium Cells Cultured by Employing an Air-Liquid Interface Culture (2021)
  • Author(s): Komabayashi Kenichi、Matoba Yohei、Seto Junji、Ikeda Yoko、Tanaka Waka、Aoki Yoko、Ikeda Tatsuya、Matsuzaki Yoko、Itagaki Tsutomu、Shirato Kazuya、Mizuta Katsumi
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 74 Issue: 4 Pages: 285-292
  • DOI: 10.7883/yoken.JJID.2020.776
  • NAID: 130008066567
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2021-07-31
  • Peer Reviewed / Open Access
• [Journal Article] TMPRSS2 Activates Hemagglutinin-Esterase Glycoprotein of Influenza C Virus (2021)
  • Author(s): Sato Ko、Hayashi Hideki、Shimotai Yoshitaka、Yamaya Mutsuo、Hongo Seiji、Kawakami Kazuyoshi、Matsuzaki Yoko、Nishimura Hidekazu
  • Journal Title: Journal of Virology Volume: 95 Issue: 21
  • DOI: 10.1128/jvi.01296-21
  • Peer Reviewed / Open Access
• [Journal Article] Growth Kinetics of Influenza C Virus Antigenic Mutants That Escaped from Anti-Hemagglutinin Esterase Monoclonal Antibodies and Viral Antigenic Changes Found in Field Isolates (2021)
  • Author(s): Matsuzaki Yoko、Sugawara Kanetsu、Shimotai Yoshitaka、Kadowaki Yoko、Hongo Seiji、Mizuta Katsumi、Nishimura Hidekazu
  • Journal Title: Viruses Volume: 13 Issue: 3 Pages: 401-401
  • DOI: 10.3390/v13030401
  • Peer Reviewed / Open Access
• [Journal Article] Seasonality of Human Coronavirus OC43, NL63, HKU1, and 229E Infection in Yamagata, Japan, 2010–2019 (2020)
  • Author(s): Komabayashi Kenichi、Seto Junji、Matoba Yohei、Aoki Yoko、Tanaka Shizuka、Ikeda Tatsuya、Matsuzaki Yoko、Itagaki Tsutomu、Mizuta Katsumi
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 73 Issue: 5 Pages: 394-397
  • DOI: 10.7883/yoken.JJID.2020.525
  • NAID: 130007907189
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2020-09-30
  • Peer Reviewed / Open Access
• [Journal Article] 2011年から2013年の山形県における３つの異なる遺伝子型の肺炎マイコプラズマの地域的広がりとマクロライド耐性株出現のタイミングに関する検討 (2020)
  • Author(s): Suzuki Yu、Seto Junji、Shimotai Yoshitaka、Itagaki Tsutomu、Katsushima Yuriko、Katsushima Fumio、Ikeda Tatsuya、Mizuta Katsumi、Hongo Seiji、Matsuzaki Yoko
  • Journal Title: 山形大学紀要. 医学 : 山形医学 = Bulletin of the Yamagata University. Medical science : Yamagata medical journal Volume: 38 Issue: 1 Pages: 19-24
  • DOI: 10.15022/00004781
  • NAID: 120006796075
  • URL: https://yamagata.repo.nii.ac.jp/records/4825
  • Year and Date: 2020-02-15
  • Peer Reviewed
• [Journal Article] Longitudinal course of influenza C virus antibody titers of healthy adults in Sendai, Japan (2020)
  • Author(s): Liao Feng、Nishimura Hidekazu、Ito Hiroko、Zhang Yunhui、Matsuzaki Yoko
  • Journal Title: Journal of Clinical Virology Volume: 133 Pages: 104662-104662
  • DOI: 10.1016/j.jcv.2020.104662
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Longitudinal epidemiology of human coronavirus OC43 in Yamagata, Japan, 2010-2017: Two groups based on spike gene appear one after another (2020)
  • Author(s): Komabayashi Kenichi、Matoba Yohei、Tanaka Shizuka、Seto Junji、Aoki Yoko、Ikeda Tatsuya、Shimotai Yoshitaka、Matsuzaki Yoko、Itagaki Tsutomu、Mizuta Katsumi
  • Journal Title: Journal of Medical Virology Volume: 93 Issue: 2 Pages: 945-951
  • DOI: 10.1002/jmv.26361
  • Peer Reviewed
• [Journal Article] Antigenic changes among the predominantly circulating C/Sao Paulo lineage strains of influenza C virus in Yamagata, Japan, between 2015 and 2018 (2020)
  • Author(s): Matsuzaki Yoko、Shimotai Yoshitaka、Kadowaki Yoko、Sugawara Kanetsu、Hongo Seiji、Mizuta Katsumi、Nishimura Hidekazu
  • Journal Title: Infection, Genetics and Evolution Volume: 81 Pages: 104269-104269
  • DOI: 10.1016/j.meegid.2020.104269
  • Peer Reviewed
• [Journal Article] Polyclonal spread of multiple genotypes of Mycoplasma pneumoniae in semi-closed settings in Yamagata, Japan. (2019)
  • Author(s): Suzuki Y, Seto J, Shimotai Y, Itagaki T, Katsushima Y, Katsushima F, Ikeda T, Mizuta K, Hongo S, Matsuzaki Y.
  • Journal Title: J Med Microbiol. Volume: 68 Issue: 5 Pages: 785-790
  • DOI: 10.1099/jmm.0.000969
  • Peer Reviewed
• [Journal Article] Phylogenetic and antigenic analyses of coxsackievirus A6 isolates in Yamagata, Japan between 2001 and 2017 (2019)
  • Author(s): Mizuta Katsumi、Tanaka Shizuka、Komabayashi Kenichi、Aoki Yoko、Itagaki Tsutomu、Katsushima Fumio、Katsushima Yuriko、Yoshida Hiroshi、Ito Sueshi、Matsuzaki Yoko、Ikeda Tatsuya
  • Journal Title: Vaccine Volume: 37 Issue: 8 Pages: 1109-1117
  • DOI: 10.1016/j.vaccine.2018.12.065
  • Peer Reviewed
• [Journal Article] Cocirculation of Influenza C Viruses with Distinct Internal Genome Constellations in Iwate Prefecture, Japan, in 2016 (2018)
  • Author(s): Takahashi Masaki、Obara Takahiro、Matsuzaki Yoko、Maisawa Shun-ichi、Sasaki Yutaka、Yoshino Naoto、Shirasawa Akira、Iwabuchi Kaori、Takahashi Tomoko、Kajita Hiroko、Ono Yasushi、Ryo Akihide、Kimura Hirokazu、Muraki Yasushi
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 71 Issue: 5 Pages: 393-395
  • DOI: 10.7883/yoken.JJID.2018.204
  • NAID: 130007485681
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2018-09-30
  • Peer Reviewed / Open Access
• [Journal Article] Neutralizing Epitopes and Residues Mediating the Potential Antigenic Drift of the Hemagglutinin-Esterase Protein of Influenza C Virus (2018)
  • Author(s): Matsuzaki Yoko、Sugawara Kanetsu、Furuse Yuki、Shimotai Yoshitaka、Hongo Seiji、Mizuta Katsumi、Nishimura Hidekazu
  • Journal Title: Viruses Volume: 10 Issue: 8 Pages: 417-417
  • DOI: 10.3390/v10080417
  • Peer Reviewed / Open Access
• [Journal Article] Clinical characteristics of children infected with enterovirus D68 in an outpatient clinic and the association with bronchial asthma (2018)
  • Author(s): Itagaki Tsutomu、Aoki Yoko、Matoba Yohei、Tanaka Shizuka、Ikeda Tatsuya、Mizuta Katsumi、Matsuzaki Yoko
  • Journal Title: Infectious Diseases Volume: 50 Issue: 4 Pages: 303-312
  • DOI: 10.1080/23744235.2017.1400176
  • Peer Reviewed
• [Journal Article] Trends of Human Coronaviruses in Yamagata, Japan in 2015–2016 Focusing on the OC43 Outbreak of June 2016 (2018)
  • Author(s): Matoba Yohei、Aoki Yoko、Tanaka Shizuka、Unno Maki、Komabayashi Kenichi、Ikeda Tatsuya、Shimotai Yoshitaka、Matsuzaki Yoko、Itagaki Tsutomu、Mizuta Katsumi
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 71 Issue: 2 Pages: 167-169
  • DOI: 10.7883/yoken.JJID.2017.263
  • NAID: 130006517084
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access
• [Presentation] エスケープ変異株と自然分離株にみるC型インフルエンザウイルスの抗原変異とその選択. (2021)
  • Author(s): 松嵜葉子
  • Organizer: 第34回インフルエンザ研究者交流の会
• [Presentation] Ｃ型インフルエンザウイルスの増殖に関与するCM2細胞質領域のアミノ酸配列の解析． (2021)
  • Author(s): 下平義隆，菅原勘悦，松嵜葉子，邵力，村木靖，後藤崇成，本郷誠治
  • Organizer: 第68回日本ウイルス学会学術集会
• [Presentation] 山形県における2010～2019年の季節性コロナウイルスの疫学研究． (2021)
  • Author(s): 水田克巳，松嵜葉子
  • Organizer: 第62回日本臨床ウイルス学会
• [Presentation] 2017-2018シーズンに分離されたC型インフルエンザウイルスの系統樹解析と抗原解析． (2019)
  • Author(s): 松嵜葉子，下平義隆，本郷誠治，水田克巳，高橋雅輝，村木靖，西村秀一
  • Organizer: 第33回インフルエンザ研究者交流の会
• [Presentation] 2019年のB型インフルエンザに対するバロキサビルの効果と治療前後の耐性変異を含むウイルス検出の状況. (2019)
  • Author(s): 松嵜葉子，板垣勉，池田辰也，水田克巳
  • Organizer: 第112回日本小児科学会山形地方会
• [Presentation] Amino acid sequences of CM2 cytoplasmic domain involved in influenza C virus replication. (2019)
  • Author(s): Shimotai Y, Sugawara K, Matsuzaki Y, Sho R, Muraki Y, Goto T, Hongo S
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] 分子疫学解析法を用いた山形県における2011年から2013年の肺炎マイコプラズマ学校内および家族内感染の検討. (2019)
  • Author(s): 鈴木裕，瀬戸順次，板垣勉，池田辰也，水田克巳，本郷誠治，松嵜葉子
  • Organizer: 第68回日本感染症学会東日本地方会学術集会
• [Presentation] 2012年～2013年シーズン以降のマクロライド耐性肺炎マイコプラズマの推移. (2019)
  • Author(s): 勝島由利子，勝島史夫, 鈴木裕，瀬戸順次，田中静佳，水田克巳，松嵜葉子
  • Organizer: 第71回北日本小児科学会
• [Presentation] C 型インフルエンザウイルスの増殖に関与するCM2タンパク質の細胞質領域のアミノ酸配列. (2019)
  • Author(s): 下平義隆，菅原勘悦，松嵜葉子，邵力，村木靖，後藤崇成，本郷誠治
  • Organizer: 第73回日本細菌学会東北支部総会
• [Presentation] Mutations of residues 73-75 in the influenza C virus CM2 protein impair virus replication. (2018)
  • Author(s): Shimotai Y, Sugawara K, Matsuzaki Y, Sho R, Muraki Y, Goto T, Hongo S
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] Antigenic and genetic analyses of influenza C viruses isolated in Iwate prefecture, in 2016. (2018)
  • Author(s): Takahashi M, Matsuzaki Y, Sasaki Y, Ryo A, Kimura H, Muraki Y
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] 2001～2017年に山形で分離されたコクサッキーウイルスA6 型の分子疫学. (2018)
  • Author(s): 水田克巳，田中静佳，駒林賢一，青木洋子，池田辰也，板垣勉，勝島史夫，勝島由利子，吉田宏，伊藤末志，松嵜葉子
  • Organizer: 第72回日本細菌学会東北支部会