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Progression towards AIDS leads to increased Torque teno virus and Torque teno minivirus titers in tissues of HIV infected individuals.

Torque teno virus (TTV) and Torque teno minivirus (TTMV) are highly prevalent in the general population and although no disease has been associated with these viruses yet, co-infections with other pathological viruses are frequent. Both viruses are extremely heterogeneous, especially for DNA viruses, and the role of the immune system in controlling the infections has yet to be established. In this study the TTV/TTMV viral loads in HIV positive tissues have been investigated for the first time. The titers of both TTV and TTMV were compared in the bone marrow and spleen tissues from three groups: HIV negative individuals, HIV positive individuals and HIV positive individuals who had progressed to AIDS, leading to immunosuppression. Limiting dilution PCR using primers situated in the UTR region of the genome were used to semi-quantitate the virus, and TTV and TTMV were differentiated using melting curve analysis of the PCR product. The AIDS group had significantly higher titers compared with both the HIV positive and negative groups for both bone marrow (AIDS vs. HIV positive P = 0.006, AIDS vs. HIV negative P < 0.001) and spleen (AIDS vs. HIV positive P = 0.022, AIDS vs. HIV negative P < 0.001). Analysis of TTV/TTMV titer with CD4 T lymphocyte count showed a significant inverse correlation however neither HCV co-infection or type of Anellovirus infection (single TTV or TTMV, or mixed TTV/TTMV) showed any significant correlation with virus titer. The results show a link between deterioration of the immune system and increased the viral loads in studied tissues.

AIDS-Related Opportunistic Infections↗

Detection of swine torque teno virus in Italian pig herds.

Anellovirus is a recently created, floating genus of viruses. Torque teno virus (TTV), the type species in the genus, was first discovered in a human patient with a post-transfusion hepatitis of unknown aetiology. Recently, TTV genetically related to but distinct from those discovered in humans have also been found in animals, including pigs. The aims of this study were to estimate the prevalence of swine TTV in Italian pig herds and some risk factors possibly associated with this infection. Serum samples from 179 healthy pigs from 10 farms located in north-central Italy were tested by polymerase chain reaction for the presence of swine TTV DNA. Viral DNA was found in the sera of 43 pigs (24.0%), coming from eight of the 10 farms examined. Prevalence was significantly higher in finishing herds (40.1%) than in farrow-to-finish herds (11.0%) and did not depend on the size of the herd. Within the finishing herds the prevalence was significantly higher in weaners (57.4%) than in fatteners (22.9%), but this difference was not observed in farrow-to-finish herds. No relationship was observed between the prevalence of swine TTV and the implementation of some general hygiene practices and biosecurity procedures within the herds.

Animal Husbandry↗

Torque teno virus (TTV): current status.

Torque teno virus (TTV), currently classified into the family Circoviridae, genus Anellovirus, was first found in a patient with non-A-E hepatitis. TTV has a single stranded circular DNA of approximately 3.8 kb. TTVs are extraordinarily diverse, spanning five groups including SANBAN and SEN viruses. Torque teno mini virus (TTMV) with approximately 2.9 kb genome also has wide variants. Recently, two related 2.2- and 2.6-kb species joined this community. Recombinations between variants are frequent. This extensive TTV diversity remains unexplained; it is unclear how TTVs could be viable, and why they require such genetic variation. An unequivocal culture system is still not available. TTVs are ubiquitous in > 90% of adults worldwide but no human pathogenicity of TTV has been fully established. Epidemiological surveys need to specify the variants being studied and clinical targets, and must calibrate the sensitivity of the assay used. Potentially interesting observations include a higher viral load in patients with severe idiopathic inflammatory myopathies, cancer and lupus. Active replication was also found in infants with acute respiratory diseases. TTV/TTMV-related viruses were found in chimpanzees, apes, African monkeys and tupaias, and also in chickens, pigs, cows, sheep and dogs. Experimentally, rhesus monkeys were persistently infected by TTV, but only 1/53 chimpanzees. TTV transcribes three species of mRNAs, 3.0-, 1.2- and 1.0-kb in the ratio of 60:5:35. Recently, at least three mRNAs were shown in chicken anaemia virus. The genomic region -154/-76 contains a critical promoter. TTV seems to have at least three proteins; however, the definite functions of these proteins await further research work.

Adult↗

One-year monthly monitoring of Torque teno virus (TTV) in river water in Italy.

Torque teno virus (TTV) is prevalent worldwide in general populations but at present is not related with any specific pathology. Its presence in faeces and its remarkable environmental stability suggest the possibility of using it as an indicator of faecal contamination in the environment. To evaluate the waterborne spread of TTV and its possible relationship with human pathogen enteric viruses, water samples were collected monthly for a year (May 2004-April 2005) from a river receiving the effluent of the treatment plant of the city of Pisa, concentrated and assayed with bimolecular tests (PCR, RT-PCR). TTV was detected in three samples (25%) while 16% of samples were positive for enteroviruses, 33% for rotaviruses, 8% for noroviruses genotype 1 and 25% for noroviruses genotype 2. Only two TTV samples (June and January) were also positive for rotavirus and norovirus, respectively. The detection of TTV in water confirmed its possible faecal-oral route of transmission but data are still insufficient to draw conclusions about the role of TTV as a viral indicator.

Base Sequence↗

Deep Characterisation of Circulating Torque Teno Virus DNA Load in Crohn's Disease Patients.

Torque teno virus (TTV) DNA load in plasma is suggested as a marker for immunosuppression post-transplantation. Crohn's disease (CD) arises from genetic susceptibility, environmental factors, and dysbiosis, causing immune responses. This study examines TTV DNA load in CD patients in remission and its correlation with relapse. Using quantitative real-time polymerase chain reaction (PCR) and metagenomic analysis, the dynamic of plasma TTV DNA load was analyzed from a cohort of CD patients (n&#x2009;=&#x2009;39) over 1 year and compared with controls (n&#x2009;=&#x2009;49). At inclusion, TTV DNA was significantly higher in CD patients compare to control (Median [IQR]: 3.27 [2.43-3.67] and 2.05 [1.28-2.80] Log copies/mL, p&#x2009;=&#x2009;0.0004). Plasma TTV DNA load failed to predict disease relapse in CD patients. Augmented plasma TTV DNA levels in CD patients correlated with diminished circulating CD3&#x2009;+&#x2009;T cells and especially CD4&#x2009;+&#x2009;T cells. No preferential representation of TTV subspecies or Anelloviridae genera was detected in CD patients' plasma. This study revealed elevated TTV DNA levels in CD patients' plasma compared to healthy controls, underscoring the intriguing potential of TTV blood sampling as a biomarker in CD.

Humans↗

A multiplex PCR assay able to simultaneously detect Torque teno virus isolates from phylogenetic groups 1 to 5.

Torque teno virus (TTV) is a circular, single-stranded DNA virus that chronically infects healthy individuals of all ages worldwide. TTV has an extreme genetic heterogeneity which is reflected in its current classification into five main phylogenetic groups (1-5). Using specific PCR assays, it has been shown that many individuals are co-infected with TTV isolates belonging to different phylogenetic groups. Here, a multiplex PCR assay was developed, using five recombinant plasmids. Each plasmid carried an insert of different size issued from a TTV isolate belonging to a different group. The assay was able to simultaneously amplify DNAs of TTV isolates belonging to all five phylogenetic groups. Multiplex PCR was then tested satisfactorily on DNAs extracted from 55 serum samples (47 health care workers and 8 AIDS patients). All individuals but nine were infected with at least one TTV isolate. Co-infection with multiple isolates was found in 29/47 (62%) health care workers and in 8/8 (100%) AIDS patients. A number of discrepancies were observed when results obtained with three thermostable DNA polymerases were compared. For example, four TTV phylogenetic groups were detected in a particular serum sample by using one of the three DNA polymerases, whereas the other two enzymes were able to detect only three TTV groups. However, none of the three enzymes used could be broadly considered to be more efficient than the others. Despite its limitations, the assay described here constitutes a suitable tool to visualize the degree of co-infection of a given population, avoiding time-consuming experiments.

Acquired Immunodeficiency Syndrome↗

One-year monthly monitoring of Torque teno virus (TTV) in wastewater treatment plants in Japan.

Torque teno virus (TTV) is a novel hepatitis virus which is considered to be transmitted by the fecal-oral route. Wastewater samples were collected monthly from eight wastewater treatment plants in Japan for 1 year, from July 2003 to June 2004, and tested for the presence of TTV by TaqMan PCR. TTV was detected in 97% (93/96) of influent samples, implying that TTV is epidemic in Japan. TTV was also isolated in 18% (17/96) of secondary effluent samples before chlorination and in 24% (23/95) of final effluent samples after chlorination. There was no significant difference between the concentration of total coliform in TTV-positive final effluents and that in TTV-negative final effluents, which indicates that total coliform cannot be used as an indicator of TTV. No TTV was detected in 24 effluents for reuse from two wastewater treatment plants using sand filtration and ozonation.

Chlorine↗

Genetic relationship of Torque Teno virus (TTV) between humans and camels in United Arab Emirates (UAE).

Torque Teno Virus (TTV) species-cross infection has been documented. However, the genetic relationship between human and animal TTV remains uncertain. In this study, genotypic characterization of TTV in different Camel specimens from the United Arab Emirates (UAE) was undertaken for comparison with human UAE TTV. A total of 56 specimens: 34 sera, 14 raw, and 8 pasteurized milk samples were tested for TTV. The results showed that the rate of infection was, 38.2% (13/34), 35.7% (5/14), and 100% (8/8), for the samples of sera, raw, and pasteurized milk respectively. The 5'untranslated region (5'UTR) of 23 clones that were generated from PCR products amplified from Camel samples (three sera, three raw, and two pasteurized milk samples) were subjected to sequence analysis. The camel TTV clones were classified as genotype 11 (47.8%), group 5 (43.5%), and SENV-H or genotype 16 (8.7%) which are among the predominant genotypes found in humans in the UAE. Phylogenetic analysis of representative sequences revealed that the similarity between isolates from camels and humans is 92%-97% for the same genotypes. The data lead to the conclusion that camels and humans share a common source of TTV infection in the UAE.

Animals↗

Torque teno virus (TTV) is highly prevalent in the European wild boar (Sus scrofa).

The present study represents the first survey of Torque teno virus (TTV) prevalence in European wild boar (Sus scrofa). The prevalence of two distinct TTV genogroups in 178 Spanish wild boar sera from different geographic regions, management conditions, gender and age was determined by a nested PCR method. The overall prevalence of TTV genogroups was 84% (58% for genogroup 1 and 66% for genogroup 2), and differences between genogroup prevalence were observed depending on the geographical region analysed. Significantly higher prevalence for TTV genogroup 2 was found in fenced managed wild boar, juvenile animals and females. No other significant differences in TTV genogroup prevalence were observed. The phylogenetic analysis of nucleotide sequences obtained from the untranslated region of selected samples revealed that the same TTV genogroups are infecting wild boar and domestic pig. The results indicate that TTV is apparently ubiquitous in European wild boar populations.

Age Factors↗

Prevalence of swine Torque teno virus in post-weaning multisystemic wasting syndrome (PMWS)-affected and non-PMWS-affected pigs in Spain.

The present study was designed to investigate the prevalence of swine Torque teno virus (TTV) in post-weaning multisystemic wasting syndrome (PMWS)-affected and non-affected Spanish swine. Nested PCR (nPCR) assays to detect two distinct TTV genogroups were applied. A significantly higher prevalence of TTV infection was found in sera from PMWS-affected animals (97 %) than in sera from non-PMWS-affected animals (78 %). Whilst PMWS-affected pigs (91 %) were more likely to be infected with TTV from genogroup 2 than non-PMWS-affected swine (72 %), no such difference was observed with genogroup 1. Nucleotide sequences of nPCR products were 91-99 % identical between strains within a genogroup. In contrast, inter-genogroup sequence identities were 49-58 %. Phylogenetic analyses demonstrated that genogroups form different clusters without association with PMWS or porcine circovirus type 2 infection status of the animals. These results indicate a high prevalence of both swine TTV genogroups in Spain, being present more frequently in PMWS-affected animals than in non-PMWS-affected animals.

Animals↗

Evaluating Associations Between Ankylosing Spondylitis, Torque Teno Virus and Polymorphisms in Interleukin 6 and Vitamin D Receptor Genes.

The etiology of ankylosing spondylitis (AS) is complex and not yet fully understood. Interleukin-6 (IL-6), vitamin D and the vitamin D receptor (VDR) play an important role in modulating immune response, and Torque teno virus is considered a marker of immune status. This case-control study aimed to investigate the predisposition to AS. A total of 85 patients with AS and 100 clinically healthy individuals were included. VDR polymorphisms (rs2228570, rs1544410, rs7975232, rs731236) were genotyped using the PCR-RFLP technique, while for the IL-6 -174 G>C (rs1800795) polymorphism the tetra-primer ARMS-PCR technique was used. The presence of TTV was detected using the hemi-nested PCR technique. Our findings indicate a statistically significant association between TTV and AS (p = 0.035). C allele of both rs1800795 polymorphism in main groups (p = 0.027) and rs731236 polymorphism in women subgroups (p = 0.036) may be linked to an increased susceptibility to AS. However, none of these associations reach statistical significance after Bonferroni correction. Furthermore, within female subgroups, a significant association was found between the T allele of rs1544410 polymorphism and AS (p = 0.000038, corrected p = 0.00076). A significant association was also observed between the TT genotype of rs2228570 polymorphism, TTV and AS (p = 0.029). Haplotype analysis revealed that certain VDR haplotypes may confer either a protective effect against AS or an increased risk of developing the condition. Notably, rs1544410 polymorphism or a linked polymorphism may influence AS susceptibility. In conclusion, our data suggest that TTV and VDR polymorphisms may be associated with an increased risk of developing AS, indicating that these markers could potentially be used in the future for earlier diagnosis and more targeted treatment of the disease.

Torque teno virus↗

Rolling-circle amplification of Torque teno virus (TTV) complete genomes from human and swine sera and identification of a novel swine TTV genogroup.

Multiply primed rolling-circle amplification is a novel technology that uses bacteriophage phi29 DNA polymerase to amplify circular DNA molecules, without the need for prior knowledge of their sequences. In an attempt to detect Torque teno virus (TTV), rolling-circle amplification was used to amplify DNA extracted from eight human and four pig serum samples. All samples gave high molecular weight (>30 kb) amplification products. By restriction endonuclease digestion, these products generated DNA fragments whose sizes were consistent with those of human TTV (3.8 kb) and swine TTV (Sd-TTV; 2.9 kb) genomes. Two TTV isolates derived from a single AIDS patient, as well as two Sd-TTV isolates derived from a single pig, were characterized by complete nucleotide sequencing. One of the Sd-TTV isolates showed very low (43-45 %) nucleotide sequence similarity to the other Sd-TTV isolate and to the prototype isolate Sd-TTV31, and could be considered the prototype of a novel genogroup.

Adult↗

Application of cation-coated filter method to detection of noroviruses, enteroviruses, adenoviruses, and torque teno viruses in the Tamagawa River in Japan.

The occurrence of human enteric viruses in surface water in the Tamagawa River, Japan, was surveyed for 1 year, from April 2003 to March 2004. Sixty-four samples were collected from six sites along the river, and 500 ml of the sample was concentrated using the cation-coated filter method, which was developed in our previous study. This method showed recovery yields of 56% +/- 32% (n = 37) for surface water samples inoculated with polioviruses. More than one kind of tested virus was detected in 43 (67%) of 64 samples by TaqMan PCR. Noroviruses and adenoviruses were detected in a high positive ratio; 34 (53%), 28 (44%), and 29 (45%) of 64 samples were positive for norovirus genotype 1 and genotype 2 and adenoviruses, respectively. The mean concentrations of norovirus genotype 1 or genotype 2 determined by real-time PCR were 0.087 and 0.61 genome/ml, respectively, showing much higher values in winter (0.21 genome/ml for genotype 1 and 2.3 genomes/ml for genotype 2). Enteroviruses were detected by both direct PCR (6 of 64 samples; 9%) and cell culture PCR (2 of 64 samples; 3%). Torque teno viruses, emerging hepatitis viruses, were also isolated in three samples (5%). The concentration of total coliforms and the presence of F-specific phages showed a high correlation with the presence of viruses, which suggested that the simultaneous use of total coliforms and F-specific phages as indicators of surface water may work to monitor viral contamination.

Adenoviridae↗

High Prevalence of Torque teno (TT) virus in classical Kaposi's sarcoma.

Human herpes virus 8 infection is the primary and necessary factor in the development of Kaposi's sarcoma, but is not sufficient per se to trigger the onset of the disease. In order to search for virological cofactors associated with the occurrence of the disease, we investigated the prevalence of active infection by two newly discovered viruses, hepatitis G virus and TT virus, among patients with classical Kaposi's sarcoma. Serum of 24 patients with Mediterranean Kaposi's sarcoma was investigated using polymerase chain reaction and compared with that of 68 healthy subjects. Cutaneous samples from patients with Kaposi's sarcoma and healthy subjects were investigated for TT virus DNA. No patient had serum markers for hepatitis G virus. TT virus DNA was present in the serum of 21/24 (87.5%) patients and 32/68 (47%) controls (p=0.002). TT virus DNA was present in the lesional skin of 5/18 patients with Kaposi's sarcoma (27.7%), but not in the skin of controls. TT virus might play a role as a cofactor in the clinical emergence of Kaposi's sarcoma in patients infected with Human herpes virus 8, perhaps by immunosuppressive effects or by a common transmission pathway for these two viruses.

Adult↗

Epidemiological surveillance of human enteric viruses by monitoring of different environmental matrices.

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.

Base Sequence↗

Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder.

Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be triggered by viral infection of the brain is unknown. We used a target-enrichment, deep sequencing platform and bioinformatic pipeline named "ViroFind", for the unbiased characterization of DNA and RNA viruses in brain samples obtained from the National Neuro-AIDS Tissue Consortium. We analyzed fresh frozen post-mortem prefrontal cortex from 72 individuals without known viral infection of the brain, including 16 HIV+/SUD+, 20 HIV+/SUD-, 16 HIV-/SUD+, and 20 HIV-/SUD-. The average age was 52.3 y and 62.5% were males. We identified sequences from 26 viruses belonging to 11 viral taxa. These included viruses with and without known pathogenic potential or tropism to the nervous system, with sequence coverage ranging from 0.03 to 99.73% of the viral genomes. In SUD+ people, HIV-infection was associated with a higher total number of viruses, and HIV+/SUD+ compared to HIV-/SUD+ individuals had an increased frequency of Adenovirus (68.8 vs 0%; p<0.001) and Epstein-Barr virus (EBV) (43.8 vs 6.3%; p=0.037) as well as an increase in Torque Teno virus (TTV) burden. Conversely, in HIV+ people, SUD was associated with an increase in frequency of Hepatitis C virus, (25 in HIV+/SUD+ vs 0% in HIV+/SUD-; p=0.031). Finally, HIV+/SUD- compared to HIV-/SUD- individuals had an increased frequency of EBV (50 vs 0%; p<0.001) and an increase in TTV viral burden, but a decreased Adenovirus viral burden. These data demonstrate an unexpectedly high variety in the human brain virome, identifying targets for future research into the impact of these taxa on the central nervous system. ViroFind could become a valuable tool for monitoring viral dynamics in various compartments, monitoring outbreaks, and informing vaccine development.

Male↗

Blood levels of TT virus following immune stimulation with influenza or hepatitis B vaccine.

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.

Adult↗