Analysis of the pathogenic mechanisms of subacute sclerosing panencephalitis by use of recombinant measles viruses, and its therapeutic application

• Project/Area Number: 23591510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka City University
• Principal Investigator: AYATA Minoru 大阪市立大学, 大学院医学研究科, 講師 (90222702)
• Co-Investigator(Kenkyū-buntansha): OHGIMOTO Shinji 大阪市立大学, 大学院医学研究科, 前期研究医 (80292853) ; SAKUMA Satoru 大阪市立大学, 大学院医学研究科, 登録医 (80570605) ; OGURA Hisashi 大阪市立大学, 大学院医学研究科, 非常勤講師 (10115222)
• Co-Investigator(Renkei-kenkyūsha): KUWAMURA Mitsuru 大阪府立大学, 生命環境科学研究科, 准教授 (20244668)
• Project Period (FY): 2011-04-28 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 亜急性硬化性全脳炎 / 麻疹ウイルス / 干渉現象

Outline of Final Research Achievements

Mutations found in measles viruses derived from subacute sclerosing panencephalitis (SSPE) were evaluated for the relationship to the neurovirulence in hamsters. Functional alterations due to amino acid substitutions in the F and H proteins were commonly responsible for neurovirulence among SSPE strains. F gene mutations were also responsible for the neurovirulence of measles virus derived from measles inclusion body encephalitis (MIBE). In addition, biased hypermutation in the measles virus genome, which is frequently found in viruses from SSPE and MIBE, was experimentally induced to the viral genome in the brains of nude mice. These findings are useful for the construction of defective- or segmented-type of recombinant measles virus vectors to treat SSPE.

Research Products

• [Journal Article] Amino acid substitutions in the heptad repeat A and C regions of the F protein responsible for neurovirulence of measles virus Osaka-1 strain from a patient with subacute sclerosing panencephalitis (2016)
  • Author(s): Ayata M, Tanaka M, Kameoka K, kuwamura M, Takeuchi K, Takeda M, Kanou K, Ogura H
  • Journal Title: Virology Volume: 487 Pages: 141-149
  • DOI: 10.1016/j.virol.2015.10.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice (2014)
  • Author(s): Otani S, Ayata M, Takeuchi K, Takeda M, Shintaku H, Ogura H
  • Journal Title: Virology Volume: 462-463 Pages: 91-97
  • DOI: 10.1016/j.virol.2014.05.035
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Remarkable similarity in genome nucleotide sequences between the Schwarz FF-8 and AIK-C measles virus vaccine strains and apparent nucleotide differences in the phosphoprotein gene. (2011)
  • Author(s): Ito C, Ohgimoto S, Kato S, Sharma LB, Ayata M, Komase K, Takeuchi K, Ihara T, Ogura H.
  • Journal Title: Microbiology and Immunology Volume: 55(7) Issue: 7 Pages: 518-524
  • DOI: 10.1111/j.1348-0421.2011.00339.x
  • NAID: 10031121499
  • Peer Reviewed
• [Presentation] Determinants of neurovirulence of the Osaka-1 strain of measles virus derived from a case of subacute sclerosing panencephalitis. (2011)
  • Author(s): M. Ayata, S. Ohgimoto, M. Kuwamura, M. Tanaka, K. Takeuchi, M. Takeda, H. Ogura
  • Organizer: XV International Congress of Virology/IUMS2011
  • Place of Presentation: 札幌