Abstract: Active infection with torquetenovirus (TTV) has been associated with an increased severity of diseases in which inflammation plays a particularly important pathogenetic role. Here, we report that cloned DNA of a genogroup 4 TTV (ViPiSAL) is an activator of proinflammatory cytokine production by murine spleen cells and that the effect is mediated via toll-like receptor (TLR)9. The same DNA also increased the levels of proinflammatory cytokines induced by two well-characterized TLR9 stimulants. Finally, in silico analyses of the genomes of ViPiSAL and other TTVs revealed marked differences in the representation of CpG motifs known to be most effective at activating immune cells via TLR9. These findings demonstrate for the first time that at least one TTV isolate has the potential to stimulate and co-stimulate inflammatory responses.
Abstract: The objective of this study was to assess the ability of nanofiltration of albumin solution, prothrombin complex (PTC) and factor IX (FIX) to remove two small, non-enveloped DNA viruses, parvovirus B19 (B19V) and torque teno virus (TTV). Virus removal was investigated with down-scale experiments performed with sequential steps of 35-nm and 15-nm nanofiltrations of products spiked with virus DNA-positive sera. Viral loads were determined by real-time PCRs. The 15-nm nanofiltration removed more than 4.0 B19V log from all the products, TTV was reduced of more than 3.0 log from albumin solution and FIX by 35-nm and 15-nm nanofiltrations, respectively, being viral DNA undetectable after these treatments. Traces of TTV were still found in PTC after the 15-nm nanofiltration. In conclusion, nanofiltration can be efficacious in removing small naked viruses but, since viruses with similar features can differently respond to the treatment, a careful monitoring of large-scale nanofiltration should be performed.
Abstract: The skin is an organ that has a primary function in the tactile receptivity and also reacts significantly to emotional stimuli. The high visibility of the dermatological diseases makes the skin a privileged target for feelings and actions that reflect behavioural problems. The tendency to self-harm can be expressed with remarkable frequency through dermatological lesions; among them neurotic excoriations are a clinical frame in which patients, unlike for other ''similar'' pathologies, succeed however in recognizing their own role in the development of the cutaneous lesions. This pathology is not frequent in paediatric age; the highest statistical frequency, however, is to be found in the adolescence period of development. The authors describe a multidisciplinary, dermatological and psychological intervention on a child who intensifies a pre-existing dermatological symptom for psychological reasons.
Abstract: Few studies have been performed on the prevalence of Torque Teno Virus (TTV) infection in liver transplant (LT) recipients. The aim of this study was to assess the prevalence, viremia and genogroup pattern of TTV among LT patients and to ascertain whether TTV causes liver damage in liver transplanted patients with biochemical and histological changes of unknown origin. Twenty-five patients were evaluated before and after LT; 80 healthy subjects were considered as controls. Serum samples were serially obtained from all the patients before LT and thereafter at 3, 6 and 12 months post-transplant. Serum TTV-DNA and genogroups were assessed by PCR. Patients underwent protocol serial liver biopsies at 6 and 12 months after LT. Results were compared using the Chi-squared tests, McNemar's and Student's t-tests. TTV-DNA was found in 25/25 patients before LT and in 60/80 blood donors (P < 0.01). The TTV-DNA load increased significantly after LT (P < 0.001). TTV-DNA was significantly higher in patients on calcineurin inhibitors (CNI) and azathioprine or mycophenolate mofetil than in patients on CNI alone (P = 0.04) at 3 months after LT. Genogroup analysis showed a significant increase in genogroup 5 positivity after LT. No differences were seen in the viremia of patients compared according to their viral versus other etiologies of their liver disease before transplantation. Viremia and TTV genotype patterns did not correlate with the presence of hypertransaminasemia or histological liver damage of unknown etiology. The prevalence of TTV-DNA was significantly higher in patients with liver cirrhosis than in controls and the viral load was significantly higher after LT than beforehand. On the basis of our data, TTV does not seem to cause liver damage following LT, although larger studies with a long-term follow up are needed to confirm these findings.
Abstract: BACKGROUND: hBoV, a recently discovered parvovirus, can be present in the respiratory tract of patients with acute respiratory diseases (ARD), but its etiologic involvement in the underlying diseases is still uncertain. OBJECTIVE: To determine in a retrospective study, the prevalence of hBoV, compared with common respiratory viruses (RV), in respiratory specimens from patients with ARD. STUDY DESIGN: A total of 335 specimens obtained over 7 years were examined. Two hundred were nasal swabs from infants hospitalized for ARD, 84 were nasal swabs or bronchoalveolar lavages from adults with pneumonia, bronchopneumonia or asthma, and 51 were nasal swabs from healthy children. RESULTS: The overall rate of hBoV detection in specimens from infants with ARD, which was 4.5%, varied slightly from year to year, except for the period 2000-2002, when no specimen was positive. Unlike other RV, no seasonal variation in hBoV incidence was noted. Infants with hBoV infection suffered either from bronchiolitis or from bronchopneumonia and 5 out of 9 cases yielded no co-infecting viral pathogen. Only one sample from an adult was hBoV positive. None of the nasal swabs from healthy subjects tested hBoV-positive. CONCLUSIONS: The findings indicate that hBoV can cause ARD in infants.
Abstract: An apparently transient infection by a superimposed torquetenovirus (TTV) in a subject who already carried three different genotypes of the virus is described. The superinfection induced a rapid increase in the plasma TTV load and a decline in immunocomplexed virus. The superinfecting TTV was a novel group 2 genotype.
Abstract: BACKGROUND: The safety of human serum albumin (HSA) is of special interest with respect to virus transmission because of the wide use of this blood product as a therapeutic agent and also, added to other products, as an excipient or a stabilizer. Conflicting data are reported concerning HSA contamination by small, naked viruses such as the erythrovirus B19 (B19V) and the anellovirus torquetenovirus (TTV). This study has been performed to assess the effect of the HSA purification procedures on the viral contamination. STUDY DESIGN AND METHODS: Known concentrations of B19V and TTV virus were spiked in raw Fraction V, the starting material from fractionated human plasma for HSA purification, which was subsequently submitted to the depth filtration procedure. After spiking, B19V and TTV genome copies were determined by real-time quantitative polymerase chain reaction assays in the mixture at the end of Fraction V dissolution, to determine the virus concentration achieved, in the HSA solution after the filtration step, in the filtered postwashing fluid, and in the supernatant of resuspended Celite. RESULTS: B19V was completely adsorbed by the Celite used as a filter aid in the depth filtration process and was thus undetectable in the resulting HSA-containing fraction. In contrast, in 2 out of 3 experiments, TTV was detected in all samples. CONCLUSION: The different behavior of the two viruses might be a reflection of their different surface charge.
Abstract: BACKGROUND: The aim of the study was to evaluate the prevalence of torquetenovirus (TTV) infection in a group of children with recurrent lower respiratory tract infections and radiologic evidence of bronchiectasis. Correlations between TTV loads and severity of bronchiectasis and between TTV loads and lung function were evaluated. METHODS: In 38 subjects, high-resolution computed tomography (HRCT) and plasma tests for TTV detection and quantification were done. In 21/38 subjects, spirometry was also performed. RESULTS: TTV was found in 31/38 (81.6%) patients. The correlation between TTV loads and severity of bronchiectasis was statistically significant (r = 0.548; P = 0.01). TTV loads showed inverse correlation with FEF25-75% (r = -0.541; P = 0.011), and FEF25-75%/FVC (r = -0.512; P = 0.018). Inverse correlation was found also between severity of bronchiectasis and functional lung parameters: FEF25-75% (r = -0.635; P = 0.002), FEV1/FVC (r = -0.541; P = 0.011), and FEF25-75%/FVC (r = -0.645; P = 0.002). CONCLUSIONS: This study demonstrated the high prevalence of TTV infection in children with bronchiectasis. Moreover, we have shown a significant correlation between TTV loads and airflow limitation within the peripheral airways, as well as between severity of bronchiectasis and decrease of lung function.
Abstract: In the aim of studying possible relations between viruses detected in clinical specimens and the ones found in different environmental matrices, in the period May 2004 to April 2005, the collection of faecal samples from gastroenteritis cases and the monthly monitoring of raw and treated wastewater, river water, seawater and mussels were carried out. The viruses considered for environmental monitoring were adenovirus, rotavirus, enterovirus, norovirus, hepatitis A virus (HAV) and Torque teno virus (TTV): they were searched for with PCR and RT-PCR and confirmed by gene sequencing. Faecal coliforms and somatic coliphages' counts were also determined. The surveillance of case detected 45 positive faecal samples out of 255 (17.6%) while 35 of 56 environmental samples (62.5%) resulted positive for at least one of the considered viruses. The detection of the same viral strain in the faeces of gastroenteritis cases and in water was possible for adenovirus and rotavirus, which were also predominant in environmental matrices; thus they could be considered as a reference for risk assessment.
Abstract: Torque Teno virus (TTV) has been demonstrated to be present persistently in the blood of healthy individuals without evidence that it causes any disease process. The levels of TTV vary in patients co-infected with other viruses and there has been considerable speculation as to whether TTV contributes to pathogenesis by other viruses or if the varying levels might be related to immune activation in the host. In the present study, the load of TTV was examined in plasma and peripheral blood mononuclear cells (PBMCs) following immunization of subjects with either influenza (a recall antigen) or hepatitis B virus (HBV) (a new antigenic exposure). The results overall did not indicate a significant change in TTV titers over a 90 day observation period; however, when TTV genogroup was taken into consideration there was an increase in viral load in plasma at some time points for subjects persistently infected with genogroup 3. While this was observed in both influenza and HBV immunized subjects, the effect was more profound in HBV vaccination. Thus, it appears that exposure to a new antigen rather than a recall antigen may stimulate TTV replication more effectively. The data further suggest that investigating the interactions between TTV and its host might require to examine specifically each TTV genogroup separately in order to determine if certain TTV types have any role in disease pathogenesis.
Abstract: Fifty-nine children with well-controlled, mild to moderate persistent asthma were studied for the presence and load of torquetenovirus (TTV) in nasal fluid. Rates of TTV positivity and mean nasal TTV loads were not dissimilar to those observed in the general population and in a group of 30 age- and residence-matched healthy control children without a history of asthmatic disease. However, in the children with asthma, 3 important indices of lung function--forced expiratory flow (FEF) in which 25% and 75% of forced vital capacity (FVC) is expired (FEF(25%-75%)), forced expiratory volume in 1 s/FVC, and FEF(25%-75%)/FVC--showed an inverse correlation with nasal TTV load. Furthermore, signs of reduced airflow were more frequent in the children with asthma who had high nasal TTV loads (> or =6 log(10) DNA copies/mL of nasal fluid) than they were in those who had low nasal TTV loads (<6 log(10) DNA copies/mL of nasal fluid), despite similar therapy regimens. In contrast, the control children showed no associations between nasal TTV load and the spirometric indices. Levels of eosinophil cationic protein in sputum were also greater in the children with asthma who had higher nasal viral burdens than they were in those who had lower nasal viral burdens. These findings are the first report of TTV infection status in children with asthma and suggest that TTV might be a contributing factor in the lung impairment caused by this condition.
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.
Abstract: Children with bronchopneumonia have considerably higher Torque tenovirus (TTV) loads than do children with milder acute respiratory diseases (ARDs). Moreover, in children with ARDs, high TTV loads correlate with low percentages of circulating CD3+ and CD4+ T cells and with elevated percentages of B cells, suggesting that TTV might be immunomodulatory. Here, we show that, in children with ARDs, the presence of TTV and TTV load correlate with concentrations of serum eosinophil cationic protein. The possible mechanisms whereby TTV infection might lead to augmented activity of eosinophils and the implications for pathogenesis are discussed.
Abstract: The natural history and pathogenic potential of the recently identified TT virus (TTV) are currently a matter of intensive investigation. In an attempt to shed some light on these issues, nasal and blood specimens of 1- to 24-month-old children hospitalized with a clinical diagnosis of acute respiratory disease (ARD) were examined for the presence, load, and genetic characteristics of TTV. The results have indicated that at least in young children, the respiratory tract not only represents a route by which abundant TTV can be shed into the environment but also may be a site of primary infection and continual replication. Although we found no compelling evidence that TTV was the direct cause of ARD in some of the children studied, the average loads of TTV were considerably higher in patients with bronchopneumonia (BP) than in those with milder ARD, raising interesting questions about the pathophysiological significance of TTV at this site. Furthermore, group 4 TTV was detected almost exclusively in children with BP.
Abstract: The newly described human metapneumovirus (hMPV) is reported here to be more commonly associated with lower respiratory tract disease. The present study examined nasal swab specimens from 90 infants with acute respiratory tract infections in Pisa, Italy, over a period of three respiratory virus seasons. The incidence of infection varied in each of the 3 years, with the rates of positivity for hMPV being 7% in 2001 but 37 and 43% in 2000 and 2002, respectively. hMPV was noted to occur seasonally in a pattern typical of the frequency of occurrence of respiratory syncytial virus. More than one-half (14 of 23) of the infants infected with hMPV had bronchopneumonia. One-third (9 of 23) of the hMPV-infected patients were also infected with another respiratory virus, a relationship that has not previously been reported. Mixed infections did not account for a higher percentage of cases of bronchopneumonia than hMPV infection alone did. Furthermore, 7 of 17 infants whose plasma was also tested for hMPV RNA were demonstrated to have virus in both nasal swab and blood specimens. The study indicates that hMPV is seen as commonly as other respiratory viruses, may be associated with severe respiratory disease in infants, can establish mixed infections with other respiratory viruses, and has a seasonal occurrence.
Abstract: A group of 24 well-characterized patients doubly infected with hepatitis C virus (HCV) and TT virus (TTV) were studied to evaluate whether the loads and number or identity of the genogroups of TTV they carried could affect the response of HCV infection to interferon-alpha (IFN) treatment. The features of HCV infection in the study patients provided a fair representation of the variables that are usually found in considering patients for IFN treatment. The same was true for the features of TTV infection. In particular, plasma loads of TTV varied over a wide range in individual patients, and infection with multiple TTV genogroups was extremely frequent. TTV genogroups 1 and 3 were the most prevalent, followed by genogroups 4 and 5. The HCV response to IFN was evaluated by measuring plasma viraemia at 24 hours and 30 days after initiation of treatment. The results showed that the TTV parameters investigated had little or no impact on the response of HCV to therapy. Due to study design, these results do not exclude that the presence of a concomitant TTV infection can affect how HCV infection responds to treatment. However, they indicate that, should such effects exist, they would be independent on load and genetic features of the infecting TTV.
Abstract: Blood and gastric tissue biopsies of 34 patients with gastritis were tested for the presence of TT virus (TTV), a ubiquitous virus found in the blood of most humans. Thirty-one of these patients were TTV positive, and 27 patients had virus in both tissues. In addition, 13 of the patients who had TTV in gastric tissue were Helicobacter pylori positive. There was an association of higher TTV titers in gastric tissues of patients who were H. pylori positive than in those in whom the bacterium could not be detected. Furthermore, this association was stronger in H. pylori-positive patients with the presence of the cagA protein. Of 10 specimens in which genogroup determination was carried out in the gastric corpus, 5/5 that were H. pylori positive showed the presence of TTV genogroup 3, while for those that were H. pylori negative, 5/5 showed the presence of genogroup 1t. By contrast, genogroup 1 was found in the corpus of only one H. pylori-positive patient, and genogroup 3 in only one H. pylori-negative patient. The histological severity of gastritis did correlate significantly with loads in the gastric tissues. There was no significant difference in TTV titer in blood of patients regardless of H. pylori infection status. These findings pique interest in clarifying the role of TTV, alone or in association with H. pylori infection, in the pathogenesis of gastritis.
Abstract: TT virus (TTV) produces chronic plasma viremia in around 90% of healthy individuals of all ages and has, therefore, been proposed as a commensal human virus. We recently demonstrated that in children hospitalized for acute respiratory diseases high TTV loads were associated with severe forms of disease. Here, we report that in such children TTV loads showed an inverse correlation with the percentage of circulating total T and helper T cells and a direct correlation with the percentage of B cells. Thus, florid TTV replication might contribute to lymphocyte imbalances and, possibly, immunosuppressive effects, thus resembling related animal viruses.
Abstract: Antimutagens and anticarcinogens are known to play an important role in decreasing damages induced by oxidants. In this study, we investigated the genotoxic and antimutagenic potential of two selenium compounds (sodium selenite: Na(2)SeO(3); seleno-DL-methionine: C(5)H(11)NO(2)Se) and Vitamins A and E in yeast cells of Saccharomyces cerevisiae. An oxidative mutagen (hydrogen peroxide (H(2)O(2)), HP) was chosen as positive control. We determined the enzymatic activities involved in the protection against oxidative damages (catalase: CAT; superoxide dismutase: SOD; glutathione peroxidase: GPx) in the cytosolic extract of yeast cells. The results demonstrated that selenium compounds exerted both mutagenic and antimutagenic effect at different concentrations. Antimutagenesis was evident both in stationary and in logarithmic phase cells. Catalase, SOD, and GPx were significantly increased in the presence of all the compounds assayed. Vitamins A (retinol) and E (alpha-tocopherol) did not have toxic or mutagenic action.
Abstract: TT virus (TTV) is a recently identified widespread DNA virus of humans that produces persistent viremia in the absence of overt clinical manifestations. In an attempt to shed light on the dynamics of chronic infection, we measured the levels of TTV in the plasma of 25 persistently infected patients during the first 3 months of alpha interferon (IFN-alpha) treatment for concomitant hepatitis C virus (HCV) infection. The first significant decline of TTV loads was observed at day 3 versus day 1 for HCV. Subsequently, the loads of TTV became progressively lower in most patients, but some initial responders relapsed before the end of the follow-up, suggesting that at least in some subjects the effects of IFN on TTV can be very short-lived. No correlation between the responses of TTV and HCV to therapy was found. Fitting the viremia data obtained during the first week of treatment into previously developed mathematical models showed that TTV sustains very active chronic infections, with over 90% of the virions in plasma cleared and replenished daily and a minimum of approximately 3.8 x 10(10) virions generated per day. Low levels of TTV were occasionally detected in the peripheral blood mononuclear cells of patients who had cleared plasma viremia, thus corroborating previous results showing that these cells may support TTV replication and/or persistence.
