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Research on genomic characteristics and disease associations of a newly discovered human serum hepatitis virus (TT virus)

Research Project

Project/Area Number 10307007
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionJICHI MEDICAL SCHOOL

Principal Investigator

MAYUMI Makoto  JICHI MEDICAL SCHOOL, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (00049016)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Masaharu  JICHI MEDICAL SCHOOL, SCHOOL OF MEDICINE, ASSISTANT, 医学部, 助手 (70326841)
NISHIZAWA Tsutomu  JICHI MEDICAL SCHOOL, SCHOOL OF MEDICINE, ASSISTANT, 医学部, 助手 (30306112)
OKAMOTO Hiroaki  JICHI MEDICAL SCHOOL, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (30177092)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥28,180,000 (Direct Cost: ¥26,500,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2001: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2000: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1999: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 1998: ¥6,700,000 (Direct Cost: ¥6,700,000)
KeywordsTT virus / TTV / circular single-stranded DNA / genotype / phylogenetic group / PCR / liver disease / extrahepatic disease / TTウイルス(TTV) / 複製中間体 / TTV DNA量 / 特発性肺線維症 / 電子顕微鏡像 / チンパンジー感染実験 / TTV抗体 / DNAウイルス / 超可変領域 / 血清肝炎 / 塩基配列 / TTウイルス抗体 / 遺伝子変異
Research Abstract

In 1997, we isolated a novel DNA virus from the serum of a patient with posttransfusion acute hepatitis of unknown etiology. It was named TT virus (TTV) after the initials (TT) of the index patient. TTV is an unenveloped, small, spherical particle with a diameter of 30-32 nm, with a circular, single-stranded DNA genome of approximately 3.8 kilobases (kb). TTV has a characteristic genomic organization and unique transcription profile. It has a wide range of sequence divergence for a DNA virus, and at least 29 genotypes have been identified, being classified further into five distantly related groups (Groups 1-5). Circular double-stranded TTV DNA in the replicative intermediate form was detected in various tissues of infected individuals, including liver tissues, bone marrow cells and lung tissues.
Although TTV infection is prevalent among healthy individuals and although infected individuals have TV (s) of one or more of various genotypes, it is true that infection with the prototype TTV (genotype 1) or other TTVs detectable by N22 PCR (Group 1) is associated with an elevated serum ALT levels in some infected humans. Transmission studies of TTV of genotype la to a chimpanzee indicated that TTV has hepatitis-inducing capacity, and that it induces elevation of the serum ALT and α-GST levels as well as histological changes in liver tissues. Therefore, it is likely that certain genotypes of TTV or some strains of TTV cause hepatitis in some clinical and epidemiological settings.
As TTV replicates not only in the liver but also in other tissues such as the bone marrow and lung tissue, TTV infection may also be associated with diseases other than hepatitis. Therefore, detailed cross-sectional and longitudinal studies are required to address the exact role of TTV in children and adults with cryptogenic liver disease or other diseases that are currently of unknown etiology.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Okamoto H, et al.: "Molecular cloning and characterization of a novel DNA virus(TTV) associated with posttransfusion hepatitis of unknown etiology"Hepatol Res. 10. 1-16 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H, et al.: "Fecal excretion of a nonenveloped DNA virus(TTV) associated with posttransfusion non-A-G hepatitis"J Med Virol. 56. 128-132 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H, et al.: "Marked heterogeneity and frequent mixed infection of TT virus demonstrated by PCR with primers from coding and noncoding regions"Virology. 259. 428-436 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H, et al.: "Circular double-stranded forms of TT virus DNA in the liver"J Virol. 74. 5161-5167 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh Y, et al.: "Visualization of TT virus particles recovered from the sera and feces of infected humans"Biochem Biophys Res Commun. 279. 718-724 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H, et al.: "Heterogeneous distribution of TT virus of distinct genotypes in multiple tissues from infected humans"Virology. 288. 358-368 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H. et al.: "Molecular cloning and characterization of a novel DNA virus (TTV) associated with posttransfusion hepatitis of unknown etiology"Hepatol Res. 10. 1-16 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H. et al.: "Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A-G hepatitis"J Med Virol. 56. 128-132 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H. et al.: "Marked heterogeneity and frequent mixed infection of TT virus demonstrated by PCR with primers from coding and noncoding regions"Virology. 259. 428-436 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H. et al.: "Circular double-stranded forms of TT virus DNA in the liver"J Virol. 74. 5161-5167 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh Y. et al.: "Visualization of TT virus particles recovered from the sera and feces of infected humans"Biochem Biophys Res Commun. 279. 718-724 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H. et al.: "Heterogeneous distribution of TT virus of distinct genotypes in multiple tissues from infected humans"Virology. 288. 358-368 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamoto H.: "TT virus : virological and genomic characteristics and disease associations"Journal of Gastroenterology. 36. 519-529 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okamoto H.: "Heterogeneous distribution of TT virus of distinct genotypes in multiple tissues from infected humans"Virology. 288. 358-368 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuda F.: "IgM-class antibodies to TT virus (TTV) in patients with acute TTV infection"Hepatology Research. 19. 1-11 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shibayama T.: "Inverse relationship between the titre of TT virus DNA and the CD4 cell count in patients infected with HIV"AIDS. 15. 563-570 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Bando M.: "Infection of TT virus in patients with idiopathic pulmonary fibrosis"Respiratory Medicine. 95. 935-942 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tokita H.: "Influence of TT virus on histopathological features of nonalcoholic fatty liver disease"Hepatology Research. 19. 197-211 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okamoto H.: "Species-specific TT viruses and cross-species infection in nonhuman primates"Journal of Virology. 74・3. 1132-1139 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okamoto H.: "Circular double-stranded forms of TT virus DNA in the liver"Journal of Virology. 74・11. 5161-5167 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okamoto H.: "Sequestration of TT virus of restricted genotypes in peripheral blood mononuclear cells"Journal of Virology. 74・21. 10236-10239 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ukita H.: "The entire nucleotide sequences of two distinct TT virus (TTV) isolates (TJN01 and TJN02) remotely related to the original TTV isolates"Archives of Virology. 145. 1543-1559 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tawara A.: "Transmission of human TT virus of genotype 1a to chimpanzees with fecal supernatant or serum from patients with acute TTV infection"Biochemical and Biophysical Research Communications. 278. 470-476 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Itoh Y.: "Visualization of TT virus particles recovered from the sera and feces of infected humans"Biochemical and Biophysical Research Communications. 279. 718-724 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okamoto H: "Marked genomic heterogeneity and frequent mixed infection of TT virus demonstrated by PCR with primers from coding and noncoding regions"Virology. 259. 428-436 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto H: "The entire nucleotide sequence of a TT virus isolate from the United States (TUS01) : comparison with reported isolates and phylogenetic analysis"Virology. 259. 437-448 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishizawa T: "Quasispecies of TT virus (TTV) with sequence divergence in hypervariable regions in the capsid protein in chronic TTV infection"J Virol. 73(11). 9604-9608 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda H: "Infection with an unenveloped DNA virus (TTV) in the patients with acute or chronic liver disease of unknown etiology and in those positive for hepatitis C virus RNA"J Hepatol. 30. 205-212 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ukita M: "Excretion into bile of an unenveloped DNA virus (TT virus) associated with acute and chronic non-A to G hepatitis"J Infect Dis. 179(5). 1245-1248 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Itho K: "Infection with an unenveloped DNA virus associated with non-A to G hepatitis in Japanese blood donors with or without elevated ALT levels"Transfusion. 39. 522-526 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto H.: "Molecular cloning and characterization of a novel DNA virus(TTV)associated with posttransfusion hepatitis of unknown etiology." Hepatol Res. 10. 1-16 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okamoto H.: "Fecal excretion of a nonenveloped DNA virus(TTV)associated with posttransfusion non-A-G hepatitis." J Med Virol. 56. 128-132 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka H.: "Infection with an unenveloped DNA virus(TTV)associated with posttransfusion non-A to G hepatitis in hepatitis patients and healthy blood donors in Thailand." J Med Virol. 56. 234-238 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikeda H.: "Infection with an unenveloped DNA virus(TTV) in the patients with acute or chronic liver disease of unknown etiology and in those positive for hepatitis C virus RNA." J Hepatol. 30. 205-212 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okamoto H.: "Distnict genotypes of a nonenveloped DNA virus associated with posttransfusion non-A to G hepatitis(TT virus) in plasma and peripheral blood mononuclear cells." J Med Virol. 57. 252-258 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuda F.: "Determination of antibodies to TT virus and application to blood donors and patients with posttransfusion non-A to G hepatitis in Japan." J Virol Methods. 77. 199-206 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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