Relationships between Total Plasma Load of Torquetenovirus (TTV) and TTV Genogroups Carried

Abstract

In 239 torquetenovirus-positive people, multiple-genogroup infections were common and associated with higher viral loads than would be expected from simple additive effects. The latter observation was restricted to the infections which included both genogroups 1 and 3, pointing to the possible existence of some kind of infection facilitation between these genogroups.Torquetenovirus (TTV), formerly known as TT virus, was discovered in 1997 by Japanese workers in the blood of a patient with cryptogenetic hepatitis and has since been shown to sustain long-term, possibly permanent viremia in a surprisingly high proportion (around 80%) of the general population worldwide (1-3, 5, 12, 13). It is also clearly documented that the loads of TTV (viral load [VL]) in plasma may differ extensively among individual hosts (15). Due to its high genetic heterogeneity, TTV is currently subdivided into five highly divergent genogroups, designated 1 to 5 (4, 14). Although multiple-genogroup TTV infections are quite frequent (1, 6, 7), there have been no reported studies on the possible relationships between the number of genogroups carried and the total VL present in an individual.In the course of our studies, we noted that individuals with high VLs tended to yield more TTV genogroups than those with low VLs. Thus, in preliminary work, we examined whether this might be due to the fact that high VLs permitted detection of TTV genogroups which escaped detection in low-VL plasma because they represented a small fraction of the total VL. The experiments did not support this explanation. In particular, the processing of five low-VL plasma specimens that had yielded one or two TTV genogroups in such a way as to augment 10-and 100-fold the amount of DNA examined in the typing assays had little or no impact on the number of genogroups detected. Similarly, when five specimens positive for four genogroups and with VLs between 6.1 and 6.8 log 10 copies per ml were diluted 100-fold, i.e., to a point where the VLs were in the range that is associated mostly with single-genogroup infections, they still yielded three to four TTV genogroups (data not shown).Such failure to provide an easy explanation for the observation prompted a systematic look at the issue. To this purpose, we assessed the presence, load, and genogroup(s) of TTV in plasma samples from 300 people. The methods have been previously reported (8, 9, 15). Briefly, extracted DNA was assayed for TTV presence and load with a universal TaqMan real-time PCR having the potential to detect and quantitate all hitherto-recognized genetic forms of the virus (8, 9). TTVpositive DNA extracts were then typed with five distinct genogroup-specific PCRs, as described previously (8, 9), using the primer sets shown in Table 1. TTV was detected in 267 people (89%) and successfully typed in 239. Most TTV-positives carried two distinct genogroups, followed by one, three, and four. TTV genogroups 1 and 3 were the most prevalent, followed at a distance by genogroups 4 and 5, while genogroup 2 was rather in...

Potential association of obesity with IL6 G-174C polymorphism and TTV infections

“…TTV is common in blood donors [68] and a high percentage of the general population exhibits chronic viraemia (around 80% in some areas) [69]. In the control group the minor alleles frequencies of IL6 G-174C (-174 C: 0.2133) [70], ACE ID (I: 0.4767) [71] and ATR1 A1166C (1166 C: 0.2967) [62,72] were in the range of data reported for other worldwide populations.…”

Role of Hematopoietic Cells in the Maintenance of Chronic Human Torquetenovirus Plasma Viremia

“…All samples from each patient were assayed in a single run and in triplicate, and at least two independent DNA extractions for each sample were examined. The DNA extracts obtained at time zero were also typed with a previously described panel of five distinct PCR assays (12), each specific for one of the genogroups into which TTVs are subdivided. At the start of the study, the patients had viral loads ranging from 4.7 to 6.8 log copies per ml of plasma and harbored between 1 and 3 TTV genogroups (Table 1).…”

Antigenic diversity and seroprevalences of Torque teno viruses in children and adults by ORF2-based immunoassays

“…We observed the highest seroprevalence rates with TTV6 LTT6 (Gr2) in children and TTV13 3h (Gr3a) in adults, this difference being either coincidental or genuinely age-specific. In comparison, PCR studies among adults have revealed TTV Gr1 and Gr3 to be the most prevalent genogroups, and Gr2 to be rare (Biagini et al, 2006;Maggi et al, 2005). The DNA prevalences of Gr1-5 were 70, 2, 73, 48 and 21 % in a French study, and 34, 2, 24, 2 and 12 % in an Italian study (Biagini et al, 2006;Maggi et al, 2005).…”

“…Seroconversions occurred, except for TTV3 HEL32, at overall rates of 5-7 % of the initial seronegative sera, whilst a number of children that were initially seropositive for a single strain later acquired multiple-genogroup antibodies. This indicates that the simultaneous presence of several TTV genogroups in the human body (de Villiers et al, 2002;Jelcic et al, 2004;Maggi et al, 2005;Niel et al, 2000;Okamoto et al, 2001) can be due to sequential infections, and that antibodies against certain TTV types are non-protective against others. Interestingly, seroreversions were seen among all TTV strains, at rates of 10-75 % of the initial seropositive children, explaining the lower seroprevalences among children aged 4-7 years.…”