Analysis on the genotype transition of measles virus prevailing in Japan - molecular bases explaining the ability of the virus to spread in the field

• Project/Area Number: 16K09112
• 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: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: ITOH MASAE 長浜バイオ大学, バイオサイエンス学部, 教授 (10201328)
• Research Collaborator: Takahashi Ken-ichi ; Wakimoto Hiroshi ; Satoh Yuto ; Sakamoto Kento
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 麻疹ウイルス / 遺伝子型 / 流行株 / 個体間伝搬 / 個体間伝播 / ウイルス排出 / 麻疹 / ウイルス / ゲノム / 感染症 / 伝播

Outline of Final Research Achievements

Measles virus (MV) is genetically highly variable and classified into 24 genotypes, whose comparison among genotypes has hardly been performed so far. Here, the growth characteristics were studied on the genotype D3- and H1-MV that caused outbreak in Japan in the late 1990s and after 2000, respectively. The growth pattern of the H1-MV absolutely differed from that of the D3-MV. The H protein of the H1-MV enhanced, but the F protein reduced the cell fusion as well as the infectious progeny virus production compared to those of the D3-MV. The results demonstrated for the first time that functional activities of MV proteins differ, leading to the specific growth characteristics depending on the genotypes. Transition of the MV genotype prevailing in an endemic area could not be explained by the antigenicity of the virus and immunized status of the residents since MV is thought to be serologically monotypic. Difference in growth characteristics might be possible to cause the transition.

Academic Significance and Societal Importance of the Research Achievements

麻疹ウイルスは、A遺伝子型のワクチンが野生株の全ての遺伝子型に対して有効で遺伝子型間で抗原性に大差がなく、遺伝子型特異的抗原性や血中抗体の保有状況など従来の疫学因子では日本国内で流行株が置換した現象を説明できない。これまで遺伝子型間で、増殖特性の比較はほとんど行われてこなかったが、本研究では、D3型とH1型で大きく異なること、ウイルス蛋白質の機能も遺伝子型で違いのあることを明らかにした。遺伝子型間でのこの違いが流行株交代を説明する可能性があり、その意義は大きい。D3型とH1型の増殖特性を決定するウイルス蛋白質の同定と機序の解明には至らず今後の課題である。

Research Products

• [Journal Article] Nonstructural protein of severe fever with thrombocytopenia syndrome phlebovirus targets STAT2 and not STAT1 to inhibit type I interferon-stimulated JAK-STAT signaling. (2018)
  • Author(s): Yoshinori Kitagawa, Madoka Sakai, Masayuki Shimojima, Masayuki Saijo, Masae Itoh, Bin Gotoh.
  • Journal Title: Microbes and Infection Volume: 20 Issue: 6 Pages: 360-368
  • DOI: 10.1016/j.micinf.2018.05.007
  • Peer Reviewed
• [Journal Article] A residue located at the junction of the head and stalk regions of measles virus fusion protein regulates membrane fusion by controlling conformational stability (2017)
  • Author(s): Yuto Satoh, Saeka Yonemori, Mitsuhiro Hirose, Hiroko Shogaki, Hiroshi Wakimoto, Yoshinori Kitagawa, Bin Gotoh, Tsuyoshi Shirai, Ken-ichi Takahashi, and Masae Itoh
  • Journal Title: Journal of General Virology Volume: 98 Issue: 2 Pages: 143-154
  • DOI: 10.1099/jgv.0.000670
  • Peer Reviewed
• [Journal Article] Human Metapneumovirus M2-2 Protein Acts as a Negative Regulator of Alpha Interferon Production by Plasmacytoid Dendritic Cells (2017)
  • Author(s): Kitagawa Yoshinori、Sakai Madoka、Funayama Mariko、Itoh Masae、Gotoh Bin
  • Journal Title: Journal of Virology Volume: 91 Issue: 20
  • DOI: 10.1128/jvi.00579-17
  • Peer Reviewed / Open Access
• [Presentation] Mutation in the matrix (M) protein is the first requirement for adaptation of the wild-type measles virus to Vero cells. (2018)
  • Author(s): Miyuki Tsunemi, Akihiko Shinoda, Yuto Satoh, Kento Sakamoto, Hiroshi Wakimoto, Miho Konami, Takumi Tsukamoto, Hiroko Shogaki, Yoshinori Kitagawa, Bin Gotoh, Ken-ichi Takahashi, Masae Itoh.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Middle East respiratory syndrome coronavirus accessory proteins that can block TLR7/9-dependent signaling leading to interferon production. (2018)
  • Author(s): Yoshinori Kitagawa, Takumi Tsukamoto, Miki Kohno, Masae Itoh, Bin Gotoh.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Measles virus fusion protein carries leucine zipper-like conformation optimized for efficient fusion induction in the HR-B domain (2017)
  • Author(s): Shogaki Hiroko、Satoh Yuto、Wakimoto Hiroshi、Kitagawa Yoshinori、Gotoh Bin、Takahashi Ken-Ichi、Itoh Masae
  • Organizer: The 65th Annual Meeting of the Japanese Society for Virology
• [Presentation] Effect of human metapneumovirus M2-2 on Toll-like receptor 7/9-dependent K63-linked polyubiquitination and phosphorylation of IRF7 (2017)
  • Author(s): Kitagawa Yoshinori、Kohno Miki、Tsukamoto Takumi、Itoh Masae、Gotoh Bin
  • Organizer: The 65th Annual Meeting of the Japanese Society for Virology
• [Presentation] Functional roles of the hemagglutinin protein of a subacute sclerosing panencephalitis (SSPE) virus, the Kobe-1 strain. (2016)
  • Author(s): Yuto Satoh, Daichi Nishikawa, Kurara, Higuchi, Da-Peng Jiang, Hiroko Shogaki, Hiroshi Wakimoto, Yoshinori Kitagawa, Bin Gotoh, Ken-ichi Takahashi, Hak Hotta, Masae Itoh.
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology.
  • Place of Presentation: Sapporo Convention Center（北海道札幌市）
  • Year and Date: 2016-10-23
• [Presentation] Effect of human metapneumovirus M2-2 protein expression on IRF7 homodimerization critical for alpha interferon gene activation. (2016)
  • Author(s): Yoshinori Kitagawa, Mariko Funayama, Madoka Sakai, Masae Itoh, Bin Gotoh.
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology.
  • Place of Presentation: Sapporo Convention Center（北海道札幌市）
  • Year and Date: 2016-10-23