Changes of DNA titer and sequence variance of TT virus in hepatic disorders

Abstract

TT virus (TTV) has been reported to occur in association with elevated alanine aminotransferase (ALT) levels in patients with posttransfusion hepatitis of unknown etiology. We examined whether the presence, change of DNA titer, or variation in sequence of this virus is associated with acute or chronic liver dysfunction in Japanese. We detected TTV by polymerase chain reaction (PCR) using primers generated from the conserved region of the TTV genome. Direct DNA sequencing of the original N22 region was used to characterize TTV isolates. We detected TTV DNA in 15 (25%) of 60 patients with liver dysfunction. Variants recovered from infected patients formed four genotypes/subtypes, corresponding to G1a, G1b, G2, and G4. Although TTV DNA titers in patients with G2 and G4 were lower than those with G1, TTV was consistently detected regardless of genotype/subtype. TTV infection continued for at least 1 year after normalization of ALT level in patients with acute liver dysfunction. Changes in DNA titer, substitutions of deduced amino acids, and variety of quasispecies of TTV were detected during the observation period, but no significant fluctuation in ALT level was found. We conclude that persistent infection, changes in DNA titer, and variation in sequence of this novel virus are not significantly related to hepatic disorders.