MOLECULAR-CLONING AND CHARACTERIZATION OF A NOVEL DNA VIRUS (TTV) ASSOCIATED WITH POSTTRANSFUSION HEPATITIS OF UNKNOWN ETIOLOGY

The genomic DNA of a novel virus named TT virus (TTV), associated with posttransfusion hepatitis of unknown etiology, was cloned from plasma of a blood donor with an elevated transaminase level but without sero logical markers of known hepatitis viruses, and its sequence of 3739 b ases was determined. TTV had a density of 1.26 g/cm(3) in sucrose, whi ch did not change after the treatment with Tween 80. The viral genome was sensitive to DNase I and Mung Bean Nuclease. Hence, TTV would be a n unenveloped, single-stranded DNA virus. Two possible open reading fr ames in different frames were identified, capable of encoding 770 and 202 amino acids, respectively. When a partial sequence of 356 bases wa s compared among TTV isolates from 78 sera from blood donors and hepat itis patients, it showed considerable divergence with differences of u p to 30%. Oligonucleotide primers were designed on two well-conserved regions for the detection of TTV DNA in serum and biopsied liver tissu es by polymerase chain reaction. TTV DNA was detected in sera from 9 o f 19 (47%) patients with fulminant hepatitis and 41 of 90 (46%) patien ts with chronic liver disease of unknown etiology. TTV DNA was detecte d in liver tissues of all the five patients tested. in titers equal or 10-100 times higher than those in the corresponding sera. These resul ts indicate that TTV would be responsible for a part of acute and chro nic liver disease of unknown etiology. (C) 1998 Elsevier Science Irela nd Ltd.