2001 Fiscal Year Final Research Report Summary
Research on genomic characteristics and disease associations of a newly discovered human serum hepatitis virus (TT virus)
| Project/Area Number |
10307007
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
MAYUMI Makoto JICHI MEDICAL SCHOOL, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (00049016)
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| 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)
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| Project Period (FY) |
1998 – 2001
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| Keywords | TT virus / TTV / circular single-stranded DNA / genotype / phylogenetic group / PCR / liver disease / extrahepatic disease |
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| 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.
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