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1996 Fiscal Year Final Research Report Summary

Studies on the mechamism of latency and reactivation of beta-herpesviruses

Research Project

Project/Area Number 06304026
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section総合
Research Field Virology
Research InstitutionOsaka University

Principal Investigator

YAMANISHI Koichi  Osaka University Med.School, Prof., 医学部, 教授 (10029811)

Co-Investigator(Kenkyū-buntansha) IHARA Seiji  Tokai University, School of Medicine, Division of Molecular Life Science, assoc., 医学部, 助教授 (50096202)
HIRAI Kanji  Medical Research Institute, Tokyo Medical and Dental University, Dept.CellRegula, 教授 (00100991)
SHIRAKI Kimiyasu  Toyama Medical and Pharmaceutical University, Dept.Virology, professor, 医学部, 教授 (50135745)
NISHIYAMA Yukihiro  Laboratory of Virology, Research Institute for Disease Mechanism and Contorol, N, 医学部, 教授 (60115615)
KURATA Takeshi  National Institute of Health, Dept.Pathology, Chairman, 感染病理部, 部長 (50012779)
Project Period (FY) 1994 – 1996
KeywordsHHV-6 / HHV-7 / Cytomegalovirus / beta-herpesvirus / Persistent infection / Latency / Reactivation / Immediate-early gene
Research Abstract

Herpesviruses (CMV,HHV-6 and HHV-7), which belong to beta-herpesvirus subfamily, infect latently in vivo after the primary infection. However the mechanism of latency and its reactivation is not clear yet. Minamishima et al.reported the seroprevalence of CMV in pregnant women in Japan, suggesting the CMV infection in Japan is still high and different from that in Europe and USA.Hirai et al.reported that the gene products of UL112/113 of CMV,which belong to early gene, are essential for DNA replication, and the appearance of antibody to pp34 correlated with the clinical symptoms after the renal transplantation. Nishiyama et al reported that the H strand of MHC class I was synthesized normally in CMV-infected cells but the transport if MHC from RES to Golgi apparatus was inhibited in infected cells. Therefore, MHC can not reach the cell membrane. Tsutsui et al.have been developing the transgenic mice by transfecting a immediate early gene of mouse CMV and trying to use it as a human model. Ihara et al.have developed humanized monoclonal antibodies which neutrakize HCMV and are going to use them for treatment of CMV infection after the organ transplantation. Shiraki et al.found anti-CMV agents in the extract of medicinal plants. Kurata et al.developed the latent system of HHV-6A in a retinal pigment epithelial cell line. Nii et al.found that HHV-7 infects persistenly in SupT1 cells. Yamanishi et al.compared the detection rate of HHV-6 and HHV-7 in saliva of healthy children by age, suggesting that HHV-7 was highly secreted even in adults. Furthemore, they analyzed an immediate early gene which may an important role for the regulation of HHV-6 gene expression.

  • Research Products

    (74 results)

All Other

All Publications (74 results)

  • [Publications] T, Yamamoto et al.: "Characterization of the UL112/113 Gene, Escential for Human Cytomegalovirus DNA Replisation," Scandinavian Jourmal of Infectious Disease. 99. 7-7 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M, Shibata et al.: "Detection of human cytomegalovirus DNA in dried new born blood filter paper," Journal of Virological Methods. 46. 279-285 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K, Takeda et al.: "Human Herpesuirus 6 Incluces IL-8 Gene Expression in Human Hepatoma Cell Live Hep G2" Journal of Medical Virology. 49. 34-40 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y, Minamishima et al.: "Role of breast milk in acquisition of cytomegalovirus infection" Microbiology and Immunology. 38. 549-552 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K, Tanaka-Taya et al,: "Seruepidemiological Study of Human Herpesvirus-6 and -7 in children of Diffevort Ages and detection of These Two Viruses in Thr" Journal of Medical Virology. 48. 88-94 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R Imagi et al: "Human Hevpesvirus 6 Induces IL-8 Gene Expression in Human Hepatoma Cell Ure, Hop G2" Journal of Medical Virology. 49. 34-40 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y, tsutui et al.: "Prolonged infection of mouse brain neurons with murine cytomegalovirus after pre- and perinatal infection" Archives of Virology. 140. 1725-1736 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y, Tsutui et al.: "Developmental disorders of the mouse brain indured by murine cytomegulovirus : Animal models for cagenital cytomegalovirus infection." Pathology International. 45. 91-102 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y, Muraki et al.: "Electron Microscopic Observations of Aberrant Capsid of Psevdorahies Virus" Journal of Electron Microscop. 45. 223-231 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M, Yoshida et al.: "A method for detection of HHV-6 antigers and its use for ovaluating antiviral drugs" Journal of Virological Methods. 58. 137-143 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y, Yamashita et al.: "Calmexin Acts as Molecular Chaperone during the Folding of Glycoprotein β of Human Cytomegralovirus" Journal of Virology. 70. 2237-2246 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y, Nishiyama et al.: "Rapid Degradation of the heavy chain of class I Major Histocompatiblity Complex Antigones in the Eldoplogmic of Human Cytomegalovirus- Jofectin Cell." Journal of Virology. 68. 7933-7943 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S, Ihara et al.: "Identification of mutation sites of a temperature-sensitive mutant of HCMV DNA Polymerase activity" Archives of Virology. 137. 263-275 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S, Ihara, et al.: "Genetic analysis of clinical isolate of human cytomegalovirus erhibiting resistance against both gancicrovir and cidofovir" Archives of Virdogy. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T, Kurata et al.: "Enhanced cytopathic effect of human cytomegolovirus on a retinal pigment epithelium cell line, K-1034, by serum-free medium," Archives of Virology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T, Kurata et al.: "Human herpesvirus b varient A infection of cultured human retinal pigment epithelial cell line," (submitted).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M, Kurokawa et al.: "Prophylactic efficacy of traditional Herbal mechcines against recurrent herpes simplex virus type 1 infection from latenty Infectod garglia in mice" JOURNAL of Dermatological Science. 14. 76-84 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T-A Yakawa et al.: "Prophylatic treatment of cytomegaroiirys infection with traditional herbs" Antiviral Research. 32. 63-70 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Yamanishi., et al: "Identification of the major capsid protein gene of beta human herpesvirus 7." Virus Research. 37. 55-62 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamanishi., et al: "Human herpesvirus 6 meningoencephalitis with sequelae." The Pediatric Infectious Disease Journal. 14(3). 240-242 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamanishi., et al: "Seroepidemiological study of human herpesvirus-6 and-7 in children of different ages and of these two viruses in throat swabs by polymerase chain reaction." Journal of Medical Virology. 48. 88-94 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamanishi., et al: "Prokaryotic expression of an immediate-early gene of human herpesvirus 6 and analysis of antigen expression in human cells." Virus Research. 41. 193-200 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamanishi., et al: "Identification of a variant a-specific neutralizing epitope on glycoprotein B (gB) of human herpesvirus-6 (HHV-6)." Virology. 222. 176-183 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamanishi., et al: "Human herpesvirus 6 induces IL-8 gene expression in humanhepatoma cell line, Hep G2." Journal of Medical Virology. 49. 34-40 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurata, T., et al: "Enhanced sytopathic effect of human cytomegalovirus on a retinal pigment epithelium cell K-1034, by serum-free medium." Archives of Virology. 142. 1645-1658 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurata, T., et al: "Human herpesvirus 6 variant A infection of cultured human retinal pigment epithelium cell line." Journal of Medical Virology. 53. 105-110 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Rapid degradation of the heavy chain of class I major histocompatibility antigens in the endoplasmic reticulum of human cytomegalovirus-infected cells." Journal of Virology. 68. 7933-7943 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Further characterization of the interaction between Epstein-Barr virus DNA polymerase catalytic subunit and its accessory subunit with regard to the 3'-to-5' exonucleotic activity and stability of initiation complex at primer termini." Journal of Virology. 68. 3354-3363 (1994)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Identification of a target of US3 protein kinase of herpes simplex virus type 2." Journal of General Virology. 75. 2065-2068 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Strong enhancement of HLA class I surface expression by incomplete cytomegalovirus particle : Analysis by dual-color flow cytometry using daponin." Transplantation Proceedings. 27. 966-969 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Association of HLA-B ^<**>03 with cervical cancer in Japanese women aged 35 and youngen." Cancer. 75. 518-521 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "The US3 protein kinase of herpes simplex virus type 2 is associated with phosphorylation of the ULI2 alkaline nuclease in vitro." Archives of Virology. 140. 1637-1644 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Growth and cytopathogenicity of herpes simplex virus in a macrophage cell line, RAW264 : A good indicator of intraperitoneal pathogenicity." Microbiology and Immunology. 39. 905-909 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Immunohistochemical studies on the transneural spread of virulent herpes simplex virus type 2 and its US3 protein kinase-deficient mutant after ocukar inoculation." Microbiology and Immunology. 40. 289-294 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Calnexin acts as a molecular chaperone during the folding of glycoprotein B of human cytomegalovirus." Journal of Virology. 70. 2237-2246 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et al: "Epatein-Barr virus single-stranded DNA-binding protein : Purification, characterization, and action on DNA synthesis by the viral DNA polymerase." Virology. 222. 352-364 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y., et a: "Calnexin associates with the precursors of gylcoprortein B,C,and D of herpes simples virus type I." Virology. 225. 216-222 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama.Y: "Herpesvirus genes : Molecular basis of viral replication and pathogenicity." Nagoya Journal of Medical Science. 59. 107-119 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiraki, K., et al: "Efficary of traditional medicines in combination with acyclovir against herpes simplex virus type 1 infection in vitro and it vivo." Antiviral Res.27. 19-37 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiraki, K., et al: "Effects of traditional herbal medicines against herpes simplex virus (HSV) type 2 and acyclovir-resistant HSV type 1 in vivo and in vitro." J.Traditional Med.12. 187-194 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiraki, K., et al: "Prophylactic treatment of cytomegalovirus infection with traditional herbs." Antiviral Res.32. 63-70 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiraki, K., et al: "Prophylactic efficacy of traditional herbal medicines against recurrent herpes simplex virus type 1 infection from latently infected ganglia in mice." J.Dermatol.Sci.14. 76-84 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Detection of human cytomegalovirus DNA in dried newborn blood filter paper." J.Virol.Methods. 46. 279-285 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Fatal Epstein-Barr virus-associated hemophagocytic syndrome." Blood. 82. 3259-3264 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Epstein-Barr virus-associated gastric carcinoma and EBV-infection of the stomach." Lab.Invest.71. 73-81 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Constuction of recombinant Marek's disease virus type 1 (MDV1) expressing the Escherichia coli lacZ gene as a possible live vaccine vector : The US10 gene of MDV1 as a stable insertion site." Vaccine. 12. 953-957 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Marek's disease virus type 1-specific phosphorylated proteins pp38 and pp24 with common amino acid termini are encoded from the opposite junction regions between the long unique and inverted repeat sequences of viral genome." Virology. 200. 816-820 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Localization of virus-related genes in virus-infected cells by in situ hybridization." ICEM. 275-276 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Expression of a novel Marek's disease virus type 1 (MVD)-specific protein p40 insect cells by a baculovirus vector and in chick embryo fibroblasts infected with MDV1." Arch.Virol.137. 191-197 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Purification of full length peptide coded inunspliced cDNA of Marek's disease virus phosphorylated protein pp38 gene" Jap.J.Vet.Sci.56. 823-826 (1994)

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      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Elevated cytokine levels in synovial fluid of rheumatoid arthritis correlates with the presence of cytomegalovirus genome." Autoimmunity. 17. 333-337 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Intracellular localization and DNA binding activity of a class of viral early phosphoproteins in human fibroblasts infected with human cytomegalovirus (Towne strain)." J.gen.Virol.75. 3309-3318 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "An autopsy of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia." Pathology International.44. 850-856 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "An infantile case of CMV-induced idiopathic thrombocytopenic purpura with predominant proliferation of CALLA-positive lymphoblast in bone marrow." Acta Pediatrica Japonica. 37. 71-74 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Rapid detection of cytomegalovirus (CMV) DNA in sera, using the polymerase chain reaction (PCR) : Relationship with clinical diagnosis of CMV infection after renal transplantation." Nephron. 70. 100-103 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Detection and quantification of virus DNA in plasma of patients with Epstein-Barr virus-associated diseases." J.Clin.Microb. 33. 1765-1768 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Epstein-Barr virus (EBV) activity in patients on chronic hemodialysis." Nephron. 70. 449-454 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Increased number of Epstein-Barr virus latently infected B-cells in T-cell non-Hodgkin's lymphoma tissues." Arch.Virol.140. 1419-1426 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Characterization of the UL112/113 gene, essential for human cytomegalovirus DNA replication." Scand.J.Infect.Dis.Suppl.99. 7 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Assymmetric deletion of the junction between the short unique region and the inverted repeat does not affect viral growth in culture and vaccine-induced immunity against Marek's disease." Vaccine. 14. 277-286 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Molecular detection and differentiation of enteroviruses in endomyocardial biopsies and pericardial effusions from patients with dialated cardiomyopathy and myocarditis." Amer.Heart.J.131 (4). 760-765 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Hodgkin's disease developed in a patient with extremely high serum antibody titers against Epstein-Barr virus associated without chronic illness." J.Pediatrics Hematology/Oncology. 18 (4). 387-391 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Highly sensitive detection of latent infection by Epstein-Barr virus in peripheral blood cells of healthy individuals and in non-neoplastic tonsillar tissues from tonsillitis patient by reverse transcription-polymerase chain reaction." J.Virol.Methods.58. 81-89 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Protection of chickens from Newcastle disease by vaccination with a linear plasmid DNA expressing the F protein of Newcastle disease virus." Vaccine. 14 (8). 747-752 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: "Expression of latent membrane protein 1 (LMP1) in clinically isolated and animal models of AIDS-associated lymphomas." Pathol.Internat.46. 568-574 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ihara, S., et al: "Identification of mutations sites of a temperature-sensitive mutant of HCMV DNA polymerase activity." Arch.Virol.137. 263-275 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ihara, S., et al: "Genetic analysis of a clinical isolate of human cytomegalovirus exhibiting resistance against both gancicrovir and cidofopvir." Arch.Virol.142. 215-225 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minamishima Y., et al: "Role of breast milk in acquisition of cytomegalovirus infection." Microbaol.Immunol.38. 549-552 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nii, S., et al: "Malignant lymphoma induction in rabbits by intravenous inoculation of Epstein-Barr-Virus-related herpesvirus from HTLV-II-transformed cynomolgus leukocyte cell line (Si-IIA)." Int.J.Cancer.63. 872-880 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nii, S., et al: "A simple method for detection of HHV-6 antigens and its use for evaluating antiviral drugs." J.Virol.Methods. 58. 137-143 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nii, S., et al: "Electron microscopic observations of aberrant capsids of pseudorabies virus." J.Electron Microsc.45. 223-231 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsutsui, Y: "Developmental disorders of the mouse brain induced by murine cytomegalovirus : animal models for congenital cytomegalovirus infection." Pathol.Internat.45. 91-102 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsutsui, Y., et al: "Prolonged infection of mouse brain neurons with murine cytomegalovirus after pre-and perinatal infection." Arch.Virol.140. 1725-1736 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirai., et al: Marek's disease virus type 1 (MDV1) as a poultry vaccine vector. Vaccine 95. Cold spring Harbor Laboratory Press, 299-304 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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