[TTV: a new hepatitis virus? Transfusion-transmitted virus]

Following the discovery of hepatitis C virus (HCV), it was clear that a proportion of cases with acute and chronic hepatitis are still negative for all known viral markers, which prompted investigations to search for new hepatitis agents. In 1997 investigators in Japan isolated a DNA clone of a novel human virus using a representation difference analysis from serum samples from a patient (TT) with post-transfusion hepatitis of unknown etiology and designated TTV for transfusion-transmitted virus. TTV DNA is common in populations at increased risk for infection with hemophilia or maintenance hemodialysis and abusers of intravenous drugs. As a nonenveloped virus with a linear, single stranded genomic DNA, TTV resembles the Parvoviridae among known animal viruses. TTV has been reported in association with post-transfusion and acute and chronic hepatitis of unknown etiology. Phylogenetic analysis indicated six different genotypes of TTV with distinct subtypes [correction of sottotypes]. Viral DNA can be detected in plasma but also in liver tissue of infected subjects, suggesting that it is hepatotropic. TTV can be transmitted parenterally by blood and blood products and probably also non-parenterally by a fecal-oral route. TTV DNA is present in a large proportion of patients with different forms of non-A-G hepatitis. A new simple genotyping assay based on a restriction fragment length polymorphism of TTV was developed. This system will provide the framework for future detailed epidemiological and clinical investigations.