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Analysis of Neurovirulence of Japanese encephalitis virus based on Eprotein-receptor interaction

Research Project

Project/Area Number 04454204
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionTOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCES

Principal Investigator

YASUI Kotaro  Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学・総合研究所・研究部門, 参事研究員 (90073080)

Co-Investigator(Kenkyū-buntansha) SUGAMATA Masami  Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学, 流動研究員 (00091041)
MIYAMOTO Michiko  Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学, 主任 (40190821)
KIMURA-KURODA Junko  Tokyo Metoropolitan Institute for Neurosciences, 微生物学・免疫学, 主任 (20142151)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsJapanese encephalitis virus / neurovirulence / neuron / cellular receptor / E protein / prM protein / エンベロープ / E-Mヘテロ2量体 / E蛋白のホモ3量体 / レセプター分子 / 感受性 / 細胞受容体 / M蛋白 / preM蛋白 / E蛋白構造
Research Abstract

Factors which participated in the pathogenicity of Japanese encephalitis virus were analyzed.
The following results were obtained using primary rat brain culture and established cell lines. 1. Japanese encephalitis virus could infect and replicate in neurons but not in glial cells. 2. Japanese encephalitis virus could be adsorbed and replicate on immature neurons but not on differentiated mature neurons which completed synapse formation. 3. Japanese encephalitis virus could be adsorbed and internalized effectively on susceptible cells but not on unsusceptible cells. 4. Japanese encephalitis virus could replicate in unsusceptible cells which were received the infectious RNA directly into the cytoplasm. 5. A candidate 75Kd receptor molecule which could bind with the E protein of Japanese encephalitis virus was detected and isolated from membrane fractions of susceptible cells.
The following results were obtained from an analysis on the mechanism of particle formation of Japanese encephalit … More is virus. 1. A prM-E heterodimer on an envelope was formed after expression and processing of polyprotein in ER lumen and the prM protein was processed in golgi complex and then the M-E heterodimer on the envelope was released from infected cells as a mature virion. 2. The M-E heterodimer was converted to E homotrimer under low pH conditions. 3. This structural change occurred on the E protein could induce a fusion between the envelope of the virion and cell membranes of susceptible cells after the virion and the cellular receptor binding was completed. 4. The C terminal part of prM protein had essential Hole for the formation of the prM-E heterodimer and the construction of the E protein structure and the transport of the E protein in the cells. 5. Amino acid replacements at the neutralizing epitope induced decreased neurovirulence on the virus.
These results indicate that a part of neurovirulence of Japanese encephalitis virus is determined the binding efficiency between the cellular receptor on the susceptible cells and the E protein of the virion and prM protein has a critical role on the construction of the E protein structure responsible on the reactivity with the receptor and the cell membranes. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] J.Kimura-Kuroda,et al K.Yasui: "Specific tropism of Japanise encephalitis vims for developing neurons inprimary rat brain culture" Arch.Virology. 130. 477-484 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 保井孝太郎: "フラビウイルス蛋白質のプロセシング" 蛋白質・核酸・酵素. 37. 2766-2773 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Yasui: "Strategies of Deugue Vaccine Development by W.H.O.Using New Biotechnology" Trop.Med.35. 233-241 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 保井孝太郎: "ワクチンの問題点 日本脳炎" 日本医師会雑説. 111. 1524-1529 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Sato et al K.Yasui: "High level Expression of Hie Japanese encephelitis Vines E pritein by recombinant Vaccinie Vines and Enhancement of Its Extracellular Release by the NS3 gene Product" Visology. 192. 483-490 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Kimura-Kuroda K.Nagashima K.Yasui: "Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture" Arch.Viology. 137. 81-99 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Kimura et al K.Yasui: "Analysis of Vinus-cell binding characteristics on the determination of Japanese encephalitis vines susceptibility" Arch.Virol. 139. 239-251 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Kimura-Kuroda, M.Ichikawa, A.Ogata, K.Nagashima, K.Yasui: "Specific tropism of Japanese encephalitis virus for developing neurons in primary rat brain culture" Arch.Virology. 130. 477-484 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Yasui: "Strategies of dengue vaccine development by W.H.O.using new biotechnology" Trop.Med.35. 233-241 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Sato, C.Takamura, A.Yasuda, M.Miyamoto, K.Kamogawa, K.Yasui: "High-level expression of the Japanese encephalitis virus E protein by recombinant vaccinia virus and enhancement of its extracellular release by the NS3 gene product" Virology. 192. 483-490 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Kimura-Kuroda, K.Nagashima, K.Yasui: "Inhibition of myelin formation by HIV-1 gp 120 in rat cerebral cortex culture" Arch.Virology. 137. 81-99 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Kimura, J.Kimura-Kuroda, K.Nagashima, K.Yasui: "Analysis of virus-cell binding characteristics on the determination of Japanese encephalitis virus susceptibility" Arch.Virology. 139. 239-251 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Sato.et al K.Yasui: "High-level expression of the Japanese enceplnalitis vivus Eprotein by recombinant Vaccinia vims and enhaucement of its extracellular release" Virology. 192. 483-490 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] J.Kimura-Kuroda,K.Yasui: "Inhibition of myeliu for mation by HID-1 gp120 in rat cerebral cortex culture" Arch.Virology. 137. 81-99 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Kimura et al K.Yasui: "Analysis of vines-cell biuding ekaracteristics on the determination of Japanese encephelitisvins sasceptibility" Arch Virol.139. 239-251 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 木村純子.保井孝太郎: "日本脳炎ウイルスE膜糖蛋白と神経病原性" 細胞. 26. 296-300 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 保井孝太郎: "ワクチンの問題点 日本脳炎" 日本医師会雑誌. 111. 1524-1529 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Yasui: "Strategies of Deague Vaccine Development by W.H.O.Vsing.New Biotecnnology" Trop.Med.35. 233-241 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sato,T.,Yasui,K.,et al: "High-level expression of the Japanese encephalitis virus E protein by recombinant vaccinia virus and enhancement of its extracellular release by the NS3 gene product." Virology. 192. 483-490 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kimura-Kuroda,J.,Yasui,K.,et al: "Specific tropism of Japanese encephalitis virus for developing neurons in primary rat brain culture." Archives of Virology. 130. 477-484 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yasui,K.,: "Strategies of Dengue virus vaccine development by W.H.O. using new biotechnology." Tropical Medicine. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,T.,Takamura,C.,Yasuda,A Miyamoto,M.,Kamogawa,K.,Yasui,K.,: "Highーlevel expression of the Japanese encephalitis virus E protein by recombinant vaccinia virus and enhancement of its extracellular release by the NS3 gene product" Virology. 192. 483-490 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] KimuraーKuroda,J.Ichikawa,M.,Ogata,A.,Nagashima,K.,Yasui,K.,: "Specific Tropism of Japanese encephalitis virus for developing neurons in primary rat brain culture" Archivs of Virology. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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