Development of genotyping method for TT virus (TTV) and its application to elucidation of pathogenesis.

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In 1997, we isolated a novel DNA virus from the serum of a patient with posttransfusion acute hepatitis of unknown etiology and named it TT virus (TTV) after the initials (T.T.) of the index patient. Recently, taxonomic nomenclature for TTV has been proposed by the TTV study group of the International Committee on Taxonomy of Viruses (ICTV) : head investigator of this project (H.O.) was a member of the study group. It was designated as Torque Teno virus (TTV): this name was derived from "Torque" which means the necklace, and "Tenuis" means thin, and relates to circular, single-stranded nature of its DNA genome. TTV was classified into a novel floating genus, the Anellovirus genus, which has not yet been assigned to a family. The name of the genus, Anellovirus, was derived from "anello," which means the ring, and relates to the circular nature of the DNA genome. TTV has a wide range of sequence divergence for a DNA virus, and approximately 40 genotypes have been identified. In the present study, we classified them further into five distantly related genetic groups (Groups 1-5), and developed a selective PCR method using oligonulceotide primers specific for TTVs of each of the five genetic groups to classify TTVs into the five genetic groups. Using this PCR method, we examined the prevalence of five genetic groups of TTV in relation to age. TTVs of group 4 were prevalent in early childhood, and detected most frequently in adulthood among the five known genetic groups. TTVs of group 1were detectable in infants aged> 6 months. Its frequency increased with age and was 10-15% in adulthood. TTVs of group 3 comprised the greatest number of genotypes (15 genotypes including SENV of genotypes A to H), were coinfected with TTVs of group 1 and/or TTVs of group 4 in adulthood. Presently, we have established a real-time detection method for quantitating TTVs of group 1,2,3,4 or 5 with an attempt to apply it to clinical surveys.