TT virus as a human pathogen: significance and problems

In 1997 TTV was detected using representational difference analysis (RDA) in serum of a patient with posttransfusion hepatitis unrelated to known hepatitis 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 family "Circinoviridae". Analysis of the complete DNA nucleotide sequence of TTV identified three partially overlapping open reading frames (ORFs). Neither DNA nucleotide nor corresponding amino acid sequences of TTV do show significant homologies to known sequences. TTV DNA nucleotide sequences amplified by PCR from sera of different patients show considerable sequence variations. Although the natural route of transmission of TTV is still unknown, there is clear evidence for a transmission of TTV through blood and blood products. TTV DNA can be detected in the feces of infected individuals suggesting that it may be possible to attract TTV infection from environmental sources. Since the discovery of TTV, numerous studies have investigated the prevalence of TTV infections in different human population groups all over the world. All these studies are based on PCR detection systems, but the technical aspects of the PCR systems vary significantly between the different investigators. The results of the epidemiological studies do not show a clear picture. The discovery of TTV as a viral agent and particularly the identification of a high percentage of infected carriers in the healthy human population raises the following questions: Firstly, what is the origin and molecular 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 determine the primary structure and the coding capacity of several TTV patient isolates.