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Studies on a mechanism of hantavirus persistent infection in central nervous system and immune system

Research Project

Project/Area Number 10306019
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionHokkaido University

Principal Investigator

ARIKAWA Jiro  Hokkaido University school of Medicine Professor, 医学部, 教授 (10142704)

Co-Investigator(Kenkyū-buntansha) MORIKAWA Shigeru  National Institute of Infectious Disease Section of Virology Chief, ウイルス第一部外来性ウイルス室, 室長(研究職) (00167686)
KARIWA Hiroaki  Hokkaido University Graduate School of Veterinary Medicine Associate Professor, 大学院・獣医学研究科, 助教授 (70224714)
MORIMATSU Kumiko  Hokkaido University School of Medicine Instructor, 医学部, 助手 (90220722)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥35,600,000 (Direct Cost: ¥35,600,000)
Fiscal Year 2000: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1999: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1998: ¥24,000,000 (Direct Cost: ¥24,000,000)
KeywordsHemorrhagic fever with renal syndrome / HFRS / hantavirus / zoonosis / virus infection / pathogenicity / genetic reassortant / infection enhancement
Research Abstract

1. Hantavirus infection was enhanced about 10 times by addition of lectins (DBA and SBA) which specifically bind to N-acetylgalactosamine. This enhancement was considered to caused by the cross linking between receptor to virion by the lectins.
2. Two Vero E6 cell subclones, one induce low pH dependent cell fusion after hantavirus infection and the other resistant to cause cell fusion, were established. By using the two cell clones, the possible role for the cellular factor for responsible for induce infected cell fusion was considered.
3. After peripheral infection of hantavirus to mice, virulent virus reached to brain 4 to 5 days earlier than that of avirulent virus. This difference was considered as a mechanism which define the virulence of hantavirus in the mouse model.
4. Virulent hantavirus showed higher growth rate in the brain micro vascular cells and peritoneal macrophage, suggesting that virulence relates to the growth ability in the target organs.
5. Genetic reassortant virus between virulent and avirulent viruses were established. The comparison of the virulence of the reassortant viruses indicated that one amino acid difference at enveloped protein and nucleotide difference in the polymerase gene are related to the virulence.
6. Virulent hantavirus infected SCID mice were passively transferred with spleen cells of immunized BALB/c mice 3 weeks after infection. The recipient SCID mice represented apparent weight loss 4 days after the transfer, indicating the immune mediated pathogenicity.
7. Hantaan virus S and M genome segment which encoding nucleocapsid protein and enveloped glycoprotein, respectively were cloned and expressed in the mammalian cells.
8. Entire L genome segment which encodes polymerase was cloned. The expression of the L clone is under going.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (65 results)

All Other

All Publications (65 results)

  • [Publications] Morii,M. et al: "Antigenic characterization of Hantaan and Seoul virus nucleocapsid protein expressed by recombinant baculovirus"Journal of Clinical Microbiology. 36. 2514-2521 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kikuchi,M, et al: "Characterization of Neutralizing Monoclonal Antibody Escape Mutants of Hantaan Virus 76118."Archives of Virology. 143(1). 73-83 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kariwa,H. et al: "Urine-associated horizontal transmission of seoul virus among rats"Archives of Virology. 143. 365-374 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kariwa,H. et al: "Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East Russia."Virus Research. 59(2). 219-228 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lee,B.H. et al: "Hantavirus infection of SD rats reared in domestic laboratory animal facilities."Korean J.of the Lab.Anim.Sci.. 15(1). 49-52 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogino,M. et al: "N-acetylgalactosamine (GalNAc)-specific lectins mediate enhancement of Hantaan virus infection."Archives of Virology. 144. 1765-1777 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 森川茂,倉根一郎: "ウイルス性出血熱、職場の感染症を防ぐ;食中毒・結核から海外赴任者の健康管理まで"中央労働災害防止協会. 103-104 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Utama,A. et al: "Identification and characterization of the RNA helicase activity of japanese encephalitis virus NS3 protein."FEBS Lett.. 7;465(1). 74-78 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 有川二郎: "動物由来感染症としてのハンタウイルス感染症"日獣会誌. 52. 225-229 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saijo,M. et al: "Nucleotide sequence of thymidine kinase gene of sequencial acyclovir-resistant herpes simplex virus type 1 recovered from a child with Wiskott-Aldrich syndrome."Journal of Medical Virology. 58(4). 387-393 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Amano,H. et al: "Identification of the canarypox virus thymidine kicase gene and insertion of foreign genes."Virology. 256. 280-290 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Terajima,M. et al: "High Levels of Viremia in Patients with the Hantavirus Pulmonary Syndrome."The Journal of Infectious Diseases. 180. 2030-2034 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kariwa,H. et al.: "Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan."Microbiology and Immunology. 44(5). 357-362 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ebihara,K. et al.: "Pathogenicity of Hantaan Virus in Newborn Mice : Genetic Reassortant Study demonstrating that a Single Amino Acid Change in Glycoprotein G1 is related to Virulence."Journal of Virology. 74(19). 9245-9255 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang,H. et al: "Genetic Diversity of Hantaviruses Isolated in China and Characterization of Novel Hantaviruses Isolated from Niviventer confucianus and Rattus rattus."Virology. 278. 332-345 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murphy,M.E., et al.: "In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus."Archives of Virology. 145. 1571-1582 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi,M. et al.: "Hepatic Copper Accumulation Induces DNA Strand Breaks in the Liver Cells of Long-Evans Cinnamon Strain Rats"Biochemical and Biophysical Research Communications. 276. 174-178 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jin,H.K. et al.: "Mouse Mx2 protein inhibits Hantavirus but not Influenza virus replication."Virology. 146. 41-49 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizutani,T. et al: "The mechanism of actinomycin D-mediated increase of Borna disease virus (BDV) RNA in cells persistently infected by BDV."Microbiology and Immunology. 44(7). 597-603 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komoro,K. et al: "Characterization of monoclonal antibodies against Hokkaido strain tickborne encephalitis virus."Microbiology and Immunology. 44(6). 533-536 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saijo,M. et al: "Enzyme linked immunosolbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins."Journal of Clinical Microbiology. 39(1). 1-7 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saijo,M. et al: "Immunofluorescent method for detection of IgG antibody to Ebola virus using recombinant nucleoprotein expressed in HeLa cells by baculovirus vector."Journal of Clinical Microbiology. 39. 776-778 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morii, M.et al: "Antigenic characterization of Hantaan and Seoul virus nucleocapsid protein expressed by recombinant baculovirus."Journal of Clinical Microbiology. 36. 2514-2521 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kikuchi, M, et al: "Characterization of Neutralizing Monoclonal Antibody Escape Mutants of Hantaan Virus 76118."Archives of Virology. 143(1). 73-83 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kariwa, H.et al: "Urine-associated horizontal transmission of seoul virus among rats."Archives of Virology. 143. 365-374 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kariwa, H.et al: "Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East Russia."Virus Research. 59(2). 219-228 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lee, B.H.et al: "Hantavirus infection of SD rats reared in domestic laboratory animal facilities."Korean J.of the Lab. Anim. Sci.. 15(1). 49-52 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogino, M.et al: "N-acetylgalactosamine (GalNAc)-specific lectins mediate enhancement of Hantaan virus infection."Archives of Virology. 144. 1765-1777 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morikawa, S.et al: "Viral hemorrhagic fever, prevention of occupational infections diseases ; food poisoning. tuberculosis and health control for living in abroad."Society for the prevention of occupational hazard. 103-104 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Utama, A.et al: "Identification and characterization of the RNA helicase activity of japanese encephalitis virus NS3 protein."FEBS Lett.. 7 : 465(1). 74-78 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arikawa, J.: "Hantavirus infection as a zoonosis."The Journal of the Veterinary Medical Association. 52. 225-229 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saijo, M.et al: "Nucleotide sequence of thymidine kinase gene of sequencial acyclovir-resistant herpes simplex virus type 1 recovered from a child with Wiskott-Aldrich syndrome."Journal of Medical Virology. 58(4). 387-393 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Amano, H.et al: "Identification of the canarypox virus thymidine kicase gene and insertion of foreign genes."Virology. 256. 280-290 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Terajima, M.et al: "High Levels of Viremia in Patients with the Hantavirus Pulmonary Syndrome."The Journal of Infectious Diseases. 180. 2030-2034 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kariwa, H.et al: "Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan."Microbiology and Immunology. 44(5). 357-362 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ebihara, K.et al: "Pathogenicity of Hantaan Virus in Newborn Mice : Genetic Reassortant Study demonstrating that a Single Amino Acid Change in Glyco-protein G1 iS related to Virulence."Journal of Virology. 74(19). 9245-9255 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang, H.et al: "Genetic Diversity of Hantaviruses Isolated in China and Characterization of Novel Hantaviruses Isolated from Niviventer confucianus and Rattus rattus."Virology. 278. 332-345 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murphy, M.E.et al: "In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus."Archives of Virology. 145. 1571-1582 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi, M.et al: "Hepatic Copper Accumulation Induces DNA Strand Breaks in the Liver Cells of Long-Evans Cinnamon Strain Rats."Biochemical and Biophysical Research Communications. 276. 174-178 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jin, H.K.et al: "Mouse Mx2 protein inhibits Hantavirus but not Influenza virus replication."Virology. 146. 41-49 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizutani, T.et al: "The mechanism of actinomycin D-mediated increase of Borna disease virus(BDV) RNA in cells persistently infected by BDV."Microbiology and Immunology. 44(7). 597-603 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komoro, K.et al: "Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus."Microbiology and Immunology. 44(6). 533-536 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saijo, M.et al: "Enzyme linked immunosolbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins."Journal of Clinical Microbiology. 39(1). 1-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saijo, M.et al: "Immunofluorescent method for detection of IgG antibody to Ebola virus using recombinant nucleoprotein expressed in HeLa cells by baculovirus vector."Journal of Clinical Microbiology. 39. 776-778 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kariwa, H.et al: "Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan."Microbiology and Immunology. 44(5). 357-362 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ebihara, K.et al: "Pathogenicity of Hantaan Virus in Newborn Mice : Genetic Reassortant Study demonstrating that a Single Amino Acid Change in Glycoprotein G1 is related to Virulence."Journal of Virology. 74(19). 9245-9255 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang, H.et al: "Genetic Diversity of Hantaviruses Isolated in China and Characterization of Novel Hantaviruses Isolated from Niviventer confucianus and Rattus rattus."Virology. 278. 332-345 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murphy, M.E.et al: "In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus"Archives of Virology. 145. 1571-1582 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi, M.et al: "Hepatic Copper Accumulation Induces DNA Strand Breaks in the Liver Cells of Long-Evans Cinnamon Strain Rats"Biochemical and Biophysical Research Communications. 276. 174-178 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jin, H.K.et al: "Mouse Mx2 protein inhibits Hantavirus but not Influenza virus replication."Virology. 146. 41-49 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizutani, T.et al: "The mechanism of actinomycin D-mediated increase of Borna disease virus (BDV) RNA in cells persistently infected by BDV."Microbiology and Immunology. 44(7). 597-603 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Komoro, K.et al: "Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus."Microbiology and Immunology. 44(6). 533-536 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saijo, M.et al: "Enzyme linked immunosolbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins."Journal of Clinical Microbiology. 39(1). 1-7 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saijo, M.et al: "Immunofluorescent method for detection of IgG antibody to Ebola virus using recombinant nucleoprotein expressed in HeLa cells by baculovirus vector."Journal of Clinical Microbiology. 39. 776-778 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kariwa, H., et al.: "Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East Russia"Virus Res.. 59. 219-228 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lee, B-H., et al: "Hantavirus infection of SD rats reared in domestic laboratory animal facilities"Korean J. of the Lab. Anim. Sci.. 15(1). 49-52 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogino, M., et al.: "N-acetylgalactosamine (GalNAc)-specific lectins mediate enhancement of Hantaan virus infection"Arch, Virol.. 144. 1765-1777 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 森川茂、倉根一郎: "ウイルス性出血熱、職場の感染症を防ぐ;食中毒・結核から海外赴任者の健康管理まで"中央労働災害防止協会. 103-104 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Utama, A. et al.: "Identification and characterization of the RNA helicase activity of Japanese encephalitis virus NS3 protein"FEBS Left.. 7;465(1). 74-78 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 有川二郎: "動物由来感染症としてのハンタウイルス感染症"日獣会誌. 52. 225-229 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Saijo, M., et al.: "Nucleotide sequence of thymidine kinase gene of sequential acyclovir-resistant herpes simplex virus type 1 recovered from a child with Wiskott-Aldrich syndrome"J. Med. Virol.. 387-393 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Amano, H. et al.: "Identification of the canarypox virus thymidine kinase gene and insertion of foreign genes"Virology. 256. 280-290 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morii,M: "Antigenic characterization of Hantaan and Seoul virus nucleocapsid proteins expressed by recombinant baculovirus" Journal of Clinical Microbiology. 36. 2514-2521 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kikuchi,M: "Characterization of neutralizing monoclonal antibody escape mutants of Hantaan virus 76118" Archives of Virology. 143. 72-83 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kariwa,H: "Urine-associated horizontal transmission of Seoul virus among rats" Archives of Virology. 143. 365-374 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-11-11  

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