TT virus sequence heterogeneity in vivo: evidence for co-infection with multiple genetic types

TT virus (TTV) is a newly described DNA virus of humans that exhibits an un usually high degree of genetic heterogeneity. We have performed extensive a nalysis of the TTV populations present in samples, taken over a period of 2 to 6 years, from three individuals with persistent TTV infection, TTV DNA titres estimated for sequential samples were found to be quite stable over the entire study period in two patients, but fluctuated considerably in the third. DNA sequence analysis revealed different genetic diversity among TT V populations from samples from the three patients. In one case, absolute s equence homogeneity was observed among samples over a 3 year period. In a s econd, a limited amount of heterogeneity was found, including one sequence exhibiting G --> A hypermutation, TTV DNA sequences from the third patient exhibited quite remarkable genetic heterogeneity: evidence was found of sev en distinct infecting viruses, representing four of the six TTV genotypes t hat have been described. In addition, minor variants of three of these seve n sequences were observed, The heterogeneity of the viral population in thi s individual declined steadily over a 6 year period. This patient infected with a genetically diverse TTV population had the highest viral DNA titre.