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Studies on the mechanisms of persistent infection and reactivation of animal viruses.

Research Project

Project/Area Number 06404015
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionThe University of Tokyo

Principal Investigator

MIKAMI Takeshi  Univ.of Tokyo, Grad.Sch.of Agri.and Life Sci., Professor, 大学院・農学生命科学研究科, 教授 (20091506)

Co-Investigator(Kenkyū-buntansha) MIYAZAWA Takayuki  Univ.of Tokyo, Grad.Sch.of Agri.and Life Sci., Assistant Professor, 大学院・農学生命科学研究科, 助手 (80282705)
TOHYA Yukinobu  Kagoshima Univ., Faculty of Agriculture, Associate Professor, 農学部, 助教授 (20180119)
KAI Chieko  Univ.of Tokyo, Grad.Sch.of Agri.and Life Sci., Associate Professor, 大学院・農学生命科学研究科, 助教授 (10167330)
遠矢 幸伸  鹿児島大学, 農学部, 助教授 (30021702)
Project Period (FY) 1994 – 1999
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥28,000,000 (Direct Cost: ¥28,000,000)
Fiscal Year 1997: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1995: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1994: ¥12,300,000 (Direct Cost: ¥12,300,000)
KeywordsFIV / MDV / FHV-1 / CDV / ICP4 / immediate early transcript / B95a cells / MOLT-4 cells / 持続感染 / FIV / 腫瘍原性 / MDV / CDV / H蛋白 / F蛋白 / FHV-1 / CD8 / DNA結合蛋白 / LTR / AP-1 site / ATF site / 再活性化 / 調節遺伝子 / C / EPB結合部位 / TPA処理
Research Abstract

In persistent infection, virus can hidden in body and escape from immunological pressure, in spite of the presence of immunity. However, the virus is sometimes reactivated to produce diseases in host. Following results were obtained.
1.We established an in vitro model for a persistent infection of feline immunodeficiency virus (FIV) using a human T-lymphoid cell line (MOLT-4). FIV-specific RNA expression could not be detected in the infected MOLT-4 cells, suggesting that the viral replication was blocked in the early stage of virus life-cycle. Furthemore, it was demonstrated that infectious virus was rescued by treatment of the infected MOLT-4 cells with a phorbol ester (TPA).
2.Three specific pathogen-free cats experimentally infected with FIV subtypes A (Petaluma strain) and B (TM1 and TM2 strains) respectively were observed for over 8 years. The cat infected with FIV subtype A died with hemoperitoneum at 8 years and 8 months post-infection (p.i.), while those with FIV subtype B are st … More ill clinically healthy over 9 years p.i.. In persistent infection of FIV,the difference of pathogenicity among subtypes and the environment where animals kept were suggested to be important factors to develop AIDS.
3.Marek's disease virus (MDV) can be serologically and genetically devided into 3 serotypes and all cause persistent infection in chickens. MDV-1 is oncogenic whereas MDV-2 is non-oncogenic. To understand the mechanisms of persistent infection and oncogenicity at genetic levels, we sequenced over 90% of MDV-2 genome.
4.The immediate-early (IE) gene products of herpesviruses are thought to play an important role in regulating latent infection. We demonstrated that feline herpesvirus type 1 (FHV-1) produced a single immediate-early (IE) transcript encoding FHV-1 ICP4 and that FHV-1 ICP4 gene was alternatively regulated by the two promoters. Furthermore, it was shown that a negative regulatory element, which was composed of a 20 bp direct repeat unit, was located between the two promoters.
5.A persistently infected B95a cell line with the Yanaka strain of CDV was established. The virus recovered from this carrier culture has infectivity to fresh B95a cells, and causes persistent infection without showing CPE.This virus was designated as the Yanaka-BP strain. Immunoprecipitation revealed identical molecular mass of the H or F proteins of the Yanaka and Yanaka-BP strains. Sequence analysis of the F gene showed that the third in-frame ATG triplet which considered to be selectively required for in vitro translation of the Onderstepoort F gene was lacked in the Yanaka-BP strain. Less

Report

(5 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Kawaguchi, Y., et al.: "Nucleotide sequence and characterization of the feline herpesvirus type 1 immediate early gene." Virology. 204(1). 430-435 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawaguchi, Y., et al.: "inhibition of feline immunodeficiency virus gene expression and replication by alphaherpesvirus ICP4 homologues." Journal of General Viroligy. 75(10). 2783-2787 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawaguchi, Y., et al.: "The C/EBP site in the feline immunodeficiency virus(FIV)long terminal repeat(LTR)is necessary for its efficient replication and is also involved in the inhibition of FIV LTR-directed gene expression by pseudorabies virus ICP4." Virology. 208(2). 492-499 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyazawa, T., et al.: "Establishment of carrier-state infection of a feline renal cell line with feline syncytial virus." Journal of Veterinary Medical Science. 57(1). 65-69 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ono, M., et al: "Expression of Marek's disease virus(MDV)serotype 2 gene which has partial homology with MDV serotype 1 pp38 gene." Virus Research. 35(2). 223-229 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoshima, Y., et al.: "Roles of the auxiliary genes AP-1 binding site in the long terminal repeat feline immunodeficiency virus in the early stage of infection in cats." Journal Virology. 70(12). 8518-8526 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawaguchi, Y., et al.: "Nucleotide sequence and characterization of the feline herpesvirus type 1 immediate early gene." Virology. 204 (1). 430-435 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawaguchi, Y., et al.: "Inhibition of feline immunodeficiency virus gene expression and replication by alphaherpesvirus ICP4 homologues." J.Gen.Virol.75 (10). 2783-2787 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawaguchi, Y., et al.: "The C/EBP site in the feline immunodeficiency virus (FIV) long terminal repeat (LTR) is necessary for its efficient replication and is also involved in the inhibition of FIV LTR-directed gene expression by pseudorabies virus ICP4." Virology. 208 (2). 492-499 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyazawa, T., et al.: "Establishment of carrier-state infection of a feline renal cell line with feline syncytial virus." J.Vet.Med.Sci.57 (1). 65-69 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ono, M., et al.: "Expression of Marek's disease virus (MDV) serotype 2 gene which has partial homology with MDV serotype 1 pp38 gene." Virus Res.35 (2). 223-229 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoshima, Y., et al.: "Roles of the auxiliary genes and AP-1 binding site in the long terminal repeat of feline immunodeficiency virus in the early stage of infection in cats." J.Virol.70 (12). 8518-8526 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikeda,Y., et al.: "The effects of treatment with chemical agents or infection with feline viruses on protein-binding properties of the feline immunodeficiency virus long terminal repeat." Virus Research. 51(2). 203-212 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawaguchi,Y., et al.: "Expression of the feline herpesvirus type IICP4 gene is controlled by two alternative promoters." Archives of Virology. 142(2). 239-253 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimojima,Y., et al.: "Identification and DNA sequence analysis of the Marek's disease virus serotype 2 genes homologous to the thymidine kinase and UL 24 genes of herpes simplex virus type 1." Virus Genes. 14(1). 81-87 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamamoto,H., et al.: "Immunological and histological disorders in cats experimentally infected with feline immunodeficiency virus subtype B (TM2 strain)." Veterinary Microbiology. 57(4). 313-324 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda,Y., et al.: "Protein-binding properties of the putative AP-1 and ATF sequences in the feline immunodeficiency virus long terminal repeat." Journal of General Virology. 78(1). 95-99 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kohmoto,M., et al.: "Eight-year observation and comparative study of specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) subtypes A and B : terminal acquired immunodeficiency syndrome in a cat infected with FIV Petaluma strain." Journal of Veterinary Medical Science. 60(3). In press (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda,Y.,et.al.: "Regulatory properties of the integrated long terminal repeat of the feline immunodeficiency virus." Virus Research. 41. 201-207 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ikeda,Y.,et.al.: "Feline immunodeficiency virus can infect a human cell line (MOLT-4) but establishes a state of latency in the cells." Journal of General Virology. 77(8). 1623-1630 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inoshima,Y.,et.al.: "Persistence of high virus neutralizing antibody titers in cats experimentally infected with feline immunodeficiency virus." Journal of Veterinary Medical Science. 58(9). 925-927 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jang,H,-K.,et.al.: "Marek's disease virus serotype 2 glycoprotein I gene:Nucleotide sequence and expression by a recombinant baculovirus." Journal of Veterinary Medical Science. 58(11). 1057-1066 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kawaguchi,Y.,et.al.: "Characterization of the herpesvirus type 1 immediate early gene expression." Journal of Veterinary Medical Science. 58(8). 715-721 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ono,M.,et.al.: "Detection of Marek's disease virus serotype 1(MDV1) glycoprotein D in MDV1-infected chick embryo fibroblasts." Journal of Veterinary Medical Science. 58(8). 777-780 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kawaguchi,Y.et al.: "The C/EBP site in the feline immunodeficiency virus(FIV)long terminal repeat(LTR)is necessary for its efficient replication and is also involved in the inhibition of FIV LTR-directed gene expression by pseudorabies virus ICP4." Virology. 208. 492-499 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kawaguchi,Y.,and Mikami,T.: "Molecular interaction between retrobiruses and herpesbiruses." J.Vet.Med.Sci.57. 801-811 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kawaguchi,Y.et al.: "The feline herpesviurs type 1 ICP4 down-regulates feline immunodeficiency virus long terminal repeat(LTR)-directed gene expresion via the C/EBP site in the LTR." J.Vet.Med.Sci.57. 1129-1131 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Maeda,K.et al.: "Comparison among feline herpesvirus typel isolates by immunoblot analysis." J.Vet.Med.Sci.57. 147-150 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ono,M.et al.: "Expression of Marek's disease virus(MDV)serotype 2 gene which has partial homology with MDV serotype 1 pp38 gene." Virus Res.35. 223-229 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ono,M.et al.: "Preparation of monoclonal antibodies against Marek's disease virus serotype 1 glycoprottein D expressed by a recombinant baculovirus." Virus Res.38. 219-230 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kawaguchi,Y.et al.: "Nucleotide sequence and characterization of the feline herpesvirus type 1 immediate early gene." Virology. 204. 430-435 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kawaguchi,Y.et.al.: "Inhibition of feline immunodeficiency virus gene expression and replication by alphaherpesvirus ICP4 homologues." J.Gen.Virol.75. 2783-2787 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kawaguchi,Y.et al.: "Carrier-state infection of feline T-lymphoblastoid cells with feline calicivires." Vet.Microbiol.40. 379-386 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyazawa,T.et al.: "Growth properties of a feline immunodeficiency virus mutant which lacks an AP-1 binding site in primary peripheral blood mononuclear cells." J.Vet.Med.Sci.56. 869-872 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyazawa,T.et al.: "Comparative functional analysis of the various lentivirus long terminal repeats in human colon carcinoma cell line (SW480 cells)and feline renal cell line(CRFK cells)." J.Vet.Med.Sci.56. 895-899 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ohno,K.et al.: "Induction of apoptosis in a T lymphoblastoid cell line infected with feline immunodeficiency virus." Arch.Virol.135. 153-158 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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