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

Abstract

TT virus (TTV) is a newly described DNA virus of humans that exhibits an unusually high degree of genetic heterogeneity. We have performed extensive analysis 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 TTV populations from samples from the three patients. In one case, absolute sequence homogeneity was observed among samples over a 3 year period. In a second, 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 seven distinct infecting viruses, representing four of the six TTV genotypes that have been described. In addition, minor variants of three of these seven sequences were observed. The heterogeneity of the viral population in this individual declined steadily over a 6 year period. This patient infected with a genetically diverse TTV population had the highest viral DNA titre.

Dynamics of Persistent TT Virus Infection, as Determined in Patients Treated with Alpha Interferon for Concomitant Hepatitis C Virus Infection

“…Subsequently, HCV viremia declined at a lower rate up to day 90, when the maximum proportion of patients who had cleared the virus to an undetectable level (67%) was also observed. In accord with previous findings (4,18), in four untreated patients, monthly measurement of TTV and HCV levels in plasma showed essentially stable values, with fluctuations of no more than 0.6 and 0.5 log 10 copies/ml, respectively (data not shown). Figure 1 shows the sequential modifications of plasma TTV levels of the patients for whom a minimum of six sequential samplings were available.…”

TT Virus in the Nasal Secretions of Children with Acute Respiratory Diseases: Relations to Viremia and Disease Severity

“…As pointed out by Okamoto et al (23), the extent of TTV diversity currently recognized is already unusually great for a DNA virus but is bound to increase substantially with the accumulation of sequence data worldwide. Importantly, detection of mixed populations of TTV belonging to more than one group (up to three groups) in a single subject was a frequent finding of this and previous studies (3,9,19,28) and represents a further indication of the ubiquity and heterogeneity of TTV infection. Recent data have shown that adults can harbor different mixtures of TTV genotypes in different organs, suggestive of a preferential tropism of certain TTV strains for specific tissues (8,23,24).…”

TT virus infection: a novel virus-host relationship

“…tissues [7,13]. Recently, a group of even more divergent viruses was discovered [14,15]; these viruses show a similar genome organisation to TTV but they are quite different in nucleotide sequence and genome length; the genome of these newly discovered viruses (described as TTV-like minivirus; TLMV) is almost 1000 bases shorter (2.9 kb).…”