Involvement of host ADAR in biased hypermutation of intracelebral measles virus causing SSPE

• Project/Area Number: 14570271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Osaka City University
• Principal Investigator: OGURA Hisashi Osaka City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (10115222)
• Co-Investigator(Kenkyū-buntansha): AYATA Minoru Osaka City University, Graduate School of Medicine, Research associate, 大学院・医学研究科, 助手 (90222702) ; SETO Yoshiyuki Osaka City University, Graduate School of Medicine, Research associate, 大学院・医学研究科, 助手 (70270759) ; 松永 勇 大阪市立大学, 大学院・医学研究科, 講師 (00254425)
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: Subacute sclerosing panencephalitis / SSPE virus / Measles virus / Biased hypermutation / ADAR

Research Abstract

It has been clarified that SSPE (subacute sclerosing panencephalitis) viruses, measles virus defective variants isolated from brains of SSPE patients, acquire biased hypermutation in their M genes, in which frequent replacements from adenine to guanine in genome sense are found. Although in recent years adenosine deaminases that act on RNAs (ADARs) might be involved in its phenomenon, there has not yet been any report showing direct evidences that ADAR causes biased hypermutation of measles virus M gene. Therefore, we examined if ADAR constitutively expressed in neural cells from the externally introduced gene can induce biased hypermutation in the measles virus infected cells.
We established A172/ADAR+ cells, an ADAR constitutively expressed cell line using A172 cells, derived from human glioblastoma. These cells were infected rMV323 virus (derived from the Ichinose B strain cDNA inserted with GFP gene) or Edm-B virus (derived from the Edmonston-B strain cDNA) and incubated at 35℃ for 1 week. One half of the infected A172/ADAR+ cells were cocultured with 5 x 10^5 fresh A172/ADAR+ cells and further incubated. The other half of the infected cells were stocked at -80℃ for viral RNA analysis (RT-PCR and direct sequencing of the M gene). This way of passage were repeated 10 times. Amplification of the M gene cDNA was detected in samples of the passage 1 to 2 of rMV323 virus and of the passage 1 to 7 of Edm-B virus. At present, however, positive mutation is not suggested in the M gene.

Research Products

• [Journal Article] Probe typing of Noroviruses detected in Osaka City, Japan (2005)
  • Author(s): N.Iritani et al.
  • Journal Title: Japanese Journal of Infectious diseases 28 Pages: 53-54
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genotyping of Norovirus strains detected in outbreaks between April 2002 and March 2003 in Osaka City, Japan (2005)
  • Author(s): Y.Seto et al.
  • Journal Title: Microbiology and Infection 49 Pages: 275-283
  • NAID: 10015573205
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Probe typing of Noroviruses detected in Osaka City, Japan (2005)
  • Author(s): Iritani, N., Seto, Y., Kubo, H., Haruki, K., Murakami, T., Kaida, A., Ayata, M., Ogura, H.
  • Journal Title: Japanese Journal of Infectious diseases 58 Pages: 53-54
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genotyping of Norovirus strains detected in outbreaks between April 2002 and March 2003 in Osaka City, Japan (2005)
  • Author(s): Seto, Y., Iritani, N., Kubo, H., Kaida, A., Murakami, T., Haruki, K., Nishio, O., Ayata, M., Ogura, H.
  • Journal Title: Microbiology and Immunology 49 Pages: 275-283
  • NAID: 10015573205
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genotyping of Norovirus strains detected in outbreaks between April 2002 and March 2003 in Osaka City, Japan. (2005)
  • Author(s): Seto, Y., et al.
  • Journal Title: Microbiology and Immunology 49(3) Pages: 275-283
  • NAID: 10015573205
• [Journal Article] Probe typing of Noroviruses detected in Osaka City, Japan (2005)
  • Author(s): Iritani N., et al.
  • Journal Title: Japanese Journal of Infectious diseases 58(1) Pages: 53-54
• [Journal Article] Infection of different cell lines of neural origin with subacute sclerosing panencephalitis (SSPE) virus (2004)
  • Author(s): H.Ishida et al.
  • Journal Title: Microbiology and Immunology 48 Pages: 277-287
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Infection of different cell lines of neural origin with subacute sclerosing panencephalitis (SSPE) virus (2004)
  • Author(s): Ishida, M., Ayata, M., Shingai, M., Katayama, Y., Matsunaga, I., Seya, T., Yanagi, Y., Yamano, T., Ogura, H.
  • Journal Title: Microbiology and Immunology 48 Pages: 277-287
  • NAID: 10012840263
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Infection of different cell lines of neural origin with subacute sclerosing panencephalitis (SSPE) virus (2004)
  • Author(s): Ishida, H. et al.
  • Journal Title: Microbiology and Immunology 48(4) Pages: 277-287
• [Journal Article] Substrate Recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis (2003)
  • Author(s): D-S.Lee et al.
  • Journal Title: Journal of Biological Chemistry 278 Pages: 9761-9767
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prevalence of Norwalk virus infections in viral gastroenteritis amongchildren in Osaka City, Japan (2003)
  • Author(s): N.Iritani et al.
  • Journal Title: Journal of Clinical Microbiology 41 Pages: 1756-1759
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Receptor use by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis (2003)
  • Author(s): M.Shingai et al.
  • Journal Title: Journal of General Virology 84 Pages: 2133-2143
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mechanism of up-regulation of human Toll-like receptor (TLR) 3 secondary to infection of measles virus attenuated strains (2003)
  • Author(s): M.Tanabe et al.
  • Journal Title: Biochem. Bioph. Res. Co. 311 Pages: 39-48
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] ウイルスによる食中毒 (2003)
  • Author(s): 勢戸祥介, その他
  • Journal Title: 医薬ジャーナル 39 Pages: 1457-1461
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• [Journal Article] 亜急性硬化性全脳炎(SSPE) -麻疹ウイルスの変異と神経病原性- (2003)
  • Author(s): 綾田 稔, その他
  • Journal Title: ウイルス 53 Pages: 15-23
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Substrate Recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis (2003)
  • Author(s): Lee, D-S., Yamada, A., Sugimoto, H., Matsunaga, I., Ogura, H., Ichihara, K., Adachi, S., Park, S-Y., Shiro, Y.
  • Journal Title: Journal of Biological Chemistry 278 Pages: 9761-9767
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prevalence of Norwalk virus infections in viral gastroenteritis among children in Osaka City, Japan (2003)
  • Author(s): Iritani, N., Seto, Y., Kubo, H., Murakami, T., Haruki, K., Ayata, M., Ogura, H.
  • Journal Title: Journal of Clinical Microbiology 41 Pages: 1756-1759
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Receptor use by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis (2003)
  • Author(s): Shingai, M., Ayata, M., Ishida, H., Matsunaga, I., Katayama, Y., Seya, T., Tatsuo, H., Yanagi, Y., Ogura, H.
  • Journal Title: Journal of General Virology 84 Pages: 2133-2143
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanism of up-regulation of human Toll-like receptor (TLR) 3 secondary to infection of measles virus attenuated strains (2003)
  • Author(s): Tanabe, M., Kurita-Taniguchi, M., Takeuchi, K., Takeda, M., Ayata, M., Ogura, H., Matsumoto, M., Seya, T.
  • Journal Title: Biochemical and Biophysical Research Communications 311 Pages: 39-48
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The prevalence of Norwalk virus infections in outbreaks of acute gastroenteritis observed during the 1999-2000 season in Osaka City, Japan (2002)
  • Author(s): N.Iritani et al.
  • Journal Title: Journal of Medical Viology 66 Pages: 131-138
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Comparison of the neuropathogenicity of two SSPE sibling viruses of the Osaka-2 strain isolated with Vero and B95a cells (2002)
  • Author(s): N.Ito et al.
  • Journal Title: Journal of Neurovirology 8 Pages: 6-13
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Enzymatic reaction of hydrogen peroxide-dependent peroxygenase cytochrome P450s : kinetic deuterium isotope effects and analyses by resonance Raman spectroscopy (2002)
  • Author(s): I.Matsunaga et al.
  • Journal Title: Biochemistry 46 Pages: 1886-1892
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Delineation of the genus Sphingomonas Yabuuchi et al. 1990VP (2002)
  • Author(s): E.Yabuuchi et al.
  • Journal Title: International Journal of Systematic and Evolutionary Microbiology 52 Pages: 1485-1496
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alterations and diversity in the cytoplasmic tail of the fusion protein of subacute sclerosing panencephalitis virus (2002)
  • Author(s): X-J.Ning et al.
  • Journal Title: Virus Research 86 Pages: 123-131
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Susceptibility of human dendritic cells to measles virus depends on their activation stages in conjunction with the level of CDw150 : role of Toll stimulators in DC maturation and MV amplification (2002)
  • Author(s): N.Murabayashi et al.
  • Journal Title: Microbes and Infection 4 Pages: 785-794
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 河川水からのNorwalkウイルスの検出 (2002)
  • Author(s): 入谷展弘, その他
  • Journal Title: 生活衛生 46 Pages: 137-143
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• [Journal Article] Mutations affecting transcriptional termination in the P gene end of subacute sclerosing panencephalitis viruses (2002)
  • Author(s): M.Ayata et al.
  • Journal Title: Journal of Virology 76 Pages: 13062-13068
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional modulation of a peroxygenase cytochrome P450 : novel insight into the mechanisms of peroxygenase and peroxidase enzymes (2002)
  • Author(s): I.Matsunaga et al.
  • Journal Title: FEBS Letters 528 Pages: 90-94
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The prevalence of Norwalk virus infections in outbreaks of acute gastroenteritis observed during the 1999-2000 season in Osaka City, Japan (2002)
  • Author(s): Iritani, N., Seto, Y., Haruki, K., Kubo, H., Ayata, M., Ogura, H.
  • Journal Title: Journal of Medical Virology 66 Pages: 131-138
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Comparison of the neuropathogenicity of two SSPE sibling viruses of the Osaka-2 strain isolated with Vero and B95a cells (2002)
  • Author(s): Ito, N., Ayata, M., Shingai, M., Furukawa, K., Seto, T., Matsunaga, I., Muraoka, M., Ogura, H.
  • Journal Title: Journal of Neurovirology 8 Pages: 6-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enzymatic reaction of hydrogen peroxide-dependent peroxygenase cytochrome P450s : kinetic deuterium isotope effects and analyses by resonance Raman spectroscopy (2002)
  • Author(s): Matsunaga, I., Yamada, A., Lee, D-S., Obayashi, E., Fujiwara, N., Kobayashi, K., Ogura, H., Shiro, Y.
  • Journal Title: Biochemistry 46 Pages: 1886-1892
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Delineation of the genus Sphingomonas Yabuuchi et al. 1990VP (2002)
  • Author(s): Yabuuchi, E., Kosako, Y., Fujiwara, N., Naka, T., Matsunaga, I., Ogura, H., Kobayashi, K.
  • Journal Title: International Journal of Systematic and Evolutionary Microbiology 52 Pages: 1485-1496
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alterations and diversity in the cytoplasmic tail of the fusion protein of subacute sclerosing panencephalitis virus strains isolated in Osaka, Japan (2002)
  • Author(s): Ning, X-J., Ayata, M., Kimura, M., Komase, K., Furukawa, K., Seto, T., Ito, N., Shingai, M., Matsunaga, I., Yamano, T., Ogura, H.
  • Journal Title: Virus Research 86 Pages: 123-131
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Susceptibility of human dendritic cells to measles virus depends on their activation stages in conjunction with the level of CDw150 : role of Toll stimulators in DC maturation and MV amplification (2002)
  • Author(s): Murabayashi, N., Kurita-Taniguchi, M., Ayata, M., Matsumoto, M., Ogura, H., Seya, T.
  • Journal Title: Microbes and Infection 4 Pages: 785-794
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mutations affecting transcriptional termination in the P gene end of subacute sclerosing panencephalitis viruses (2002)
  • Author(s): Ayata, M., Komase, K., Shingai, M., Matsunaga, I., Katayama, Y., Ogura, H.
  • Journal Title: Journal of Virology 76 Pages: 13062-13068
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional modulation of a peroxygenase cytochrome P450 : novel insight into the mechanisms of peroxygenase and peroxidase enzymes (2002)
  • Author(s): Matsunaga, I., Sumimoto, T., Ayata, M., Ogura, H.
  • Journal Title: FEBS Letters 528 Pages: 90-94
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishida, H. et al.: "Infection of different cell lines of neural origin with subacute sclerosing panencephalitis (SSPE) virus"Microbiology and Immunology. (in press).
• [Publications] Tanabe, M. et al.: "Mechanism of up-regulation of human Toll-like receptor (TLR) 3 secondary to infection of measles virus attenuated strains"Biochem.Bioph.Res.Co.. 311. 39-48 (2003)
• [Publications] SHingai, M., et al.: "Receptor use by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis"Journal of General Virology. 84(8). 2133-2143 (2003)
• [Publications] Lee, D-S. et al.: "Substrate Recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis."Journal of Biological Chemistry. 278(11). 9761-9767 (2003)
• [Publications] Iritani, N. et al.: "Norwalk virus infections in viral gastroenteritis among children in Osaka City, Japan"Journal of Clinical Microbiology. 41(4). 1756-1759 (2003)
• [Publications] M.Ayata et al.: "Mutations affecting transcriptional termination in the P gene end of subacute sclerosing panencephalitis viruses"Journal of Virology. 76・24. 13062-13068 (2002)
• [Publications] N.Murabayashi et al.: "Susceptibility of human dendritic cells to measles virus depends on their activation stages in conjunction with the level of CDw150 : role of Toll stimulators in DC maturation and MV amplification"Microbes and Infection. 4. 785-794 (2002)
• [Publications] X-J.Ning et al.: "Alterations and diversity in the cytoplasmic tail of the fusion protein of subacute sclerosing panencephalitis virus"Virus Research. 86・1-2. 123-131 (2002)
• [Publications] N.Ito et al.: "Comparison of the neuropathogenicity of two SSPE sibling viruses of the Osaka-2 strain isolated with Vero and B95a cells"Journal of Neurovirology. 8・1. 6-13 (2002)