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Nucleotide sequence analysis of viral genome related with pathogenesis of dengue hemorrhagic fever

Research Project

Project/Area Number 07457078
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionNagasaki University

Principal Investigator

IGARASHI Akira  Nagasaki University, Institute of Tropical Medicine, Professor, 熱帯医学研究所, 教授 (40029773)

Co-Investigator(Kenkyū-buntansha) HASEBE Futoshi  Nagasaki University, Institute of Tropical Medicine, Research Associate, 熱帯医学研究所, 助手 (20253693)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsDengue hemorrhagic fever / Viral genome / Nucleotide sequence / Amino acid sequence / Pathogenesis / デンダ出血熱 / 3′非コード領域 / 毒力 / タイ国
Research Abstract

Comparative nucleotide and deduced amino acid sequences were analyzed for 4 dengue type 2 virus strains isolated from patients with different clinical severities in Nakhon Phanom, Northeast Thailand in 1993, in order to obtain direct evidence for virulent virus theory of the pathogenesis of dengue hemorrhagic fever.
The results showed followings : (1) Amino acid sequence of virus-specified proteins classified the isolates into 3 subtypes : subtype 1 was the isolate from the most severe DSS patient, subtype 2 were 2 isolates from DHF patients and 2 isolates from DF patients, and subtype 3 were 3 isolates from DF patients. (2) Secondary structure predicted for the 3'noncoding region (3'NCR) also classified the isolates into 3 subtypcs : subtype 1 was the isolate from DSS patient, subtype 2 were 2 isolates from DHF patients and 3 isolates from DF patients, and subtype 3 were 2 isolates from DF patients. These results indicated that the infection with virus strain possessing subtype 1 amino acid sequence and subtype 1 secondary structure of 3'NCR is expected to lead to severe clinical manifestation, while the infection with virus strains possessing subtype 3 amino acid sequence and subtype 3 secondary structure of 3'NCR is cxpected to be clinically mild. The plaque size formed on LLC-MK2 cells did not correlate with the structure of virus genome but rather with the serological response of the patients.
Further studies were carried out on comparative sequence analysis on 4 strains of dengue type 4 virus isolated in Bangkok, Thailand, 1993. The result identified strain-specific amino acid replacements for the isolate from mild DF case as well as the isolate from relatively severe DHF grade II patients. These amino acid replacements were cxpected to influence the nature of the respective proteins. Effect of the observed molecular difference on the biological characteristics of virus isolates and relation to the pathogenesis of DHF remain to be investigated.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 五十嵐 章: "デング出血熱" 最新医学-特集:新流行感染症・再流行感染症. 52. 60-67 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 五十嵐 章: "デング熱,デング出血熱" 治療学. 31. 35-39 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 五十嵐 章: "デング熱/デング出血熱" 化学療法の領域-シリーズ・目で見る感染症(45). 13. 4-5 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mangada MNM, Igarashi A: "Sequences of terminal non-coding regions from dengue-2 viruses isolated from paients exhibiting different discase severities." Virus Genes. 14. 5-12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chanyasanha C: "Nucleotide and deduced amino acid sequences of the whole structural proteins and NS1 nonstructural protein of four dengue 4 virus strains,isolated from patients in Bangkok,with different clinical severities." Jpn J Trop Med Hyg. 25. 197-207 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mangada MNM, Igarashi A: "Molecular and in vitro,analysis of cight dengue type 2 viruses isolated from patients exhibiitng different disease severities." Virology. (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 五十嵐 章: "東南アジアにおける日本脳炎とデング熱/デング出血熱" 長崎大学生涯学習教育センター運営委員会,長崎大学公開講座叢書9,アジアの時代を迎えて,II部, 212 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 五十嵐 章: "ウイルス性出血熱-ことにデング出血熱について-" 日本医学会,第108回日本医学会シンポジウム記録集,感染症, 98 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igarashi A: "Dengue hemorrhagic fever (in Japanese)" Saishi-Igaku, Special Ed.Emerging re-emerging Infectious Diseases. 52. 60-67 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igarashi A: "Dengue fever, dengue hemorrhagic fever (in Japanese)" Biomedicine & Therapeutics. 31. 35-39 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igarashi A: "Dengue fever/dengue hemorrhagic fever (in Japanese)" Antibiotics & Chemotherapy Visual Infectious Diseases (45). 13. 4-5 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mangada MNM,Igarashi A: "Sequences of terminal non-coding regions from dengue-2 viruses isolated from patients exhibiting different disease severities" Virus Genes. 14. 5-12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chanyasanha C: "Nucleotide and deduced amino acid sequences of the whole structural proteins and NS1 nonstructural protein of four dengue 4 virus strains, isolated from patients in Bangkok, with different disease severities" Japanese Journal of Tropical Medicine & Hygiene. 25. 197-207 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mangada MNM,Igarashi A: "Molecular and in vitro analysis of eight dengue type 2viruses isolated from patients exhibiting different disease severities" Virology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igarashi A: Japanese encephalitis and dengue fever/dengue hemorrhagic fever (in Japanese). Publications of Public Lecture Nagasaki University, No.9, Facing the year of Asia, Vol II,Life-long Education Center, Nagasaki University, 123-137 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igarashi A: Viral hemorrhagic fever-with special reference to dengue hemorrhagic fever (in Japanese). Proceedings of the 108th Symposium of Japan Medical Association, Infectious Diseases, 41-48 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kyaw Zin Thantほか: "Sequences of E/NS1 gene junction from four dengue-2 viruses of North-eastern Thailand and their evolutionary relationships with other dengue-2 viruses" Microbiology and Immunology. 39(8). 581-590 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kyaw Zin Thantほか: "Detection of the disease severity-related molecular differences among new Thai dengue-2 isolates in 1993,based on their structural proteins and major non-structural proten NS1 sequences" Microbiology and Immunology. 40(3). 201-216 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.N.M.Mangadaほか: "Sequences of terminal non-coding regions from four dengue-2 viruses isolated from patients exhibiting different disease severities" Virus Genes. 14(1). 5-12 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 五十嵐 章: "日本脳炎とデング熱/デング出血熱" 医学のあゆみ. 177(13). 924-929 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 五十嵐 章: "アルボウイルス性疾患-デングウイルス感染症とダニ脳炎について-" 臨床とウイルス. 24(5). 363-370 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 五十嵐 章: "デング出血熱" 最新医学. 52(1). 60-67 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 五十嵐 章: "デング熱/デング出血熱" 医薬ジャーナル社(永武毅編集「輸入感染症」), 167(6) (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kyaw Zin Thant.Morita K.Igarashi A: "Sequences of E/NS1 gene junction from four dengue-2 viruses of Northeastem Thailand and their evolutionary relationship with other denque-2 viruses" Microbiology and Immunology. 39. 581-590 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mangada MNM,ら: "Effect of incubation temperature on dengue-2 viral antigen productilonandviral RNA synthesis in infected Aedes albopictus clone C6/36 cell line" Tissue Culture Research Communication. 14. 213-220 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Chanyasanha C,ら: "Dengue virus isolation and viral genome detection by reverse transcriptase-polymerase chain reaction from serum specimens of dengue patients" Southeast Asian J Trop Med Publ Hlth. 26. 495-502 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kyaw Zin Thantら: "Detection of disease severity related molecular differences among new Thai dengue-2 isolates in 1993,based on their structural proteins and major non-structural protein NS1 sequences" Microbiology and Immunology. 40. 205-216 (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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