High prevalence of TT virus infection in healthy children and adults and in patients with liver disease in Taiwan

Abstract

A newly identified DNA virus, named TT virus (TTV), was found to be related to transfusion-associated hepatitis. We conducted the following experiments to evaluate its pathogenic role in liver disease and potential modes of transmission. We used PCR to detect TTV DNA in serum. The rates of TTV viremia in 13 patients with idiopathic acute hepatitis, 14 patients with idiopathic fulminant hepatitis, 22 patients with chronic hepatitis, and 19 patients with cirrhosis of the liver were 46, 64, 55, and 63%, respectively, and were not significantly different from those in 50 healthy control subjects (53%). PCR products derived from seven patients with liver disease and three healthy controls were cloned and then subjected to phylogenetic analyses, which failed to link a virulent strain of TTV to severe liver disease. TTV infection was further assessed in an additional 148 subjects with normal liver biochemical tests, including 30 newborns (sera collected from the umbilical cord), 23 infants, 16 preschool children, 21 individuals of an age prior to that of sexual experience (aged 6 to 15 years), 15 young adults (aged under 30 years), and 43 individuals older than 30 years. The rates of TTV viremia were 0, 17, 25, 33, 47, and 54%, respectively. These findings suggest that TTV is transmitted mainly via nonparenteral daily contact and frequently occurs very early in life and that TTV infection does not have a significant effect on liver disease.

FIG. 1

Phylogenetic analysis of the TTV isolates from Taiwan and the prototypes of Japanese isolates. N1, N2, and N3 are the isolates from three healthy individuals; A1 and A2 are the isolates from two patients with acute hepatitis; F1, F2, F3, and F4 are the isolates from four patients with fulminant hepatitis; C1 is the isolate from a patient with liver cirrhosis. J1a, J1b, J2a, and J2b are the four Japanese prototypes of genotypes 1a, 1b, 2a, and 2b, respectively (8). Sequence comparison was made for nucleotide positions 1939 to 2166 within open reading frame 1 of the TTV genome (9). The phylogenetic tree was constructed by using the computer software Clustal method with a weighted-residue weight table (DNAstar) grounded on the sequence divergence. The length of each pair of branches represents the distance between sequence pairs. The scale beneath the tree measures the distance between sequences. Units indicate the number of substitution events.