TT virus as a human pathogen: Significance and problems

In 1997 TTV was detected using representational difference analysis (RDA) i n serum of a patient with posttransfusion hepatitis unrelated to known hepa titis viruses. The genome of TTV is a circular single-stranded DNA molecule of 3852 nt with negative polarity. TTV possibly can be grouped either into the existing family Circoviridae or into a recently established virus fami ly "Circinoviridae". Analysis of the complete DNA nucleotide sequence of TT V identified three partially overlapping open reading frames (ORFs). Neithe r DNA nucleotide nor corresponding amino acid sequences of TTV do show sign ificant homologies to known sequences. TTV DNA nucleotide sequences amplifi ed by PCR from sera of different patients show considerable sequence variat ions. Although the natural route of transmission of TTV is still unknown, t here is clear evidence for a transmission of TTV through blood and blood pr oducts. TTV DNA can be detected in the feces of infected individuals sugges ting that it may be possible to attract TTV infection from environmental so urces. Since the discovery of TTV, numerous studies have investigated the p revalence of TTV infections in different human population groups all over t he world. All these studies are based on PCR detection systems, but the tec hnical aspects of the PCR systems vary significantly between the different investigators. The results of the epidemiological studies do not show a cle ar picture. The discovery of TTV as a viral agent and particularly the iden tification of a high percentage of infected carriers in the healthy human p opulation raises the following questions: Firstly, what is the origin and m olecular relatedness of TT virus. Secondly, what is the significance of TTV as a human pathogen. And thirdly, what are the exact molecular mechanisms of viral replication. To answer these questions it will be necessary to det ermine the primary structure and the coding capacity of several TTV patient isolates.