ABSTRACT
INTRODUCTION: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. METHODS: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). RESULTS: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06-10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14-5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000-1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. CONCLUSIONS: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.
Subject(s)
Cognitive Dysfunction , Frailty , Torque teno virus , Female , Aged , Humans , Aged, 80 and over , Frailty/epidemiology , Torque teno virus/physiology , Viremia/complications , Frail Elderly/psychology , Geriatric Assessment , Cognitive Dysfunction/complications , Cognitive Dysfunction/epidemiologyABSTRACT
BACKGROUND: Torquetenovirus (TTV) viremia is emerging as a promising tool to assess functional immune competence, to predict posttransplant immune-related complications, and eventually to customize immunosuppression. METHODS: In this study, 327 blood samples were tested using two real-time PCR (rtPCR) assays both targeted to the untranslated region of the TTV genome. The first assay was an in-house rtPCR developed by our group, the second one was the recently marketed TTV R-GENE assay. RESULTS: In the validation study, the TTV R-GENE showed good performances in precision and reproducibility, and sensitivity as low as 12 TTV DNA copies/mL, like previously reported for the in-house rtPCR. The Bland-Altman analysis showed that the mean difference between the two methods was -0.3 log copies/mL. In the comparison study, 69% and 72% of samples were detected positive by rtPCR and TTV R-GENE, respectively (94% concordance, κ = 0.88). Performances did not differ between the two rtPCRs by type of TTV group examined. When a newly-developed in-house digital droplet PCR was applied for TTV quantification and used as an alternative method of comparison on 94 samples, the results strongly correlated with those obtained by the two rtPCR methods (99% concordance). CONCLUSION: In summary, all the molecular methods assayed are highly sensitive and accurate in quantitation of TTV DNA in blood samples.
Subject(s)
Biomarkers/blood , DNA Virus Infections/blood , Real-Time Polymerase Chain Reaction/methods , Torque teno virus/physiology , Viremia/blood , Case-Control Studies , DNA Virus Infections/immunology , DNA, Viral/blood , Humans , Immunocompetence , Reproducibility of Results , Viremia/immunologySubject(s)
Leukemia, Promyelocytic, Acute/genetics , Oncogene Proteins, Fusion/genetics , Oncogenic Viruses/physiology , Retinoic Acid Receptor alpha , Torque teno virus/physiology , Anelloviridae/pathogenicity , Anelloviridae/physiology , Antineoplastic Agents/therapeutic use , Child , Female , Humans , Karyotype , Leukemia, Promyelocytic, Acute/pathology , Leukemia, Promyelocytic, Acute/therapy , Oncogenic Viruses/pathogenicity , Torque teno virus/pathogenicity , Tretinoin/therapeutic useABSTRACT
Torque Teno Virus (TTV) is a small, non-enveloped, single-stranded and circular DNA virus that infects the majority of the population worldwide. Increased levels of plasma TTV viral load have been observed in various situations of immune deficiency or dysregulation, and several studies have suggested that TTV levels may be inversely correlated with immune competence. The measurement of TTV viremia by qPCR has been proposed as a potential biomarker for the follow-up of functional immune competence in immunosuppressed individuals, particularly hematopoietic stem cell transplant recipients. We hypothesized that TTV viral load could be used as a prognostic marker of immune checkpoint inhibitor (ICI) efficacy, and therefore investigated the TTV viral load in melanoma patients treated with nivolumab or pembrolizumab before and after 6 months of treatment. In the present study, TTV viral load was not different in melanoma patients before anti-PD-1 introduction compared to healthy volunteers, was not modified by ICI treatment and did not allowed to distinguish patients with treatment-sensitive tumor from patients with treatment-resistant tumor.
Subject(s)
Biomarkers/analysis , DNA Virus Infections/virology , Immune Checkpoint Inhibitors/therapeutic use , Melanoma/pathology , Torque teno virus/physiology , Viral Load , Viremia/virology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Follow-Up Studies , Humans , Immunocompromised Host , Male , Melanoma/drug therapy , Melanoma/immunology , Melanoma/virology , Middle Aged , Prognosis , Retrospective Studies , Survival RateABSTRACT
Torque teno virus (TTV) is a commensal human virus observed as a circular single-negative-strand DNA molecule in various tissues and biological samples, notably in blood serum and lymphocytes. TTV has no apparent clinical significance, although it might be very useful as a prospective tool for gene delivery or as an epidemiological marker. Human populations are ubiquitously infected with TTV; the prevalence may reach 100%. The majority of babies become spontaneously infected with TTV, so that by the end of the first year of life, the prevalence reaches 'adult' values. TTV positivity in healthy early infancy and the presence of TTV in umbilical cord blood samples have been reported. The mechanism of infection and the dynamics of TTV prevalence in infants with age remain understudied. Meanwhile, the potential diagnostic and prognostic value of TTV as a marker deserves special attention and study, along with the possibility, causes and consequences of placental transmission of TTV under normal or pathological conditions.
Subject(s)
DNA Virus Infections/virology , Torque teno virus/physiology , Age Factors , DNA Virus Infections/blood , DNA Virus Infections/genetics , DNA, Viral/genetics , Female , Humans , Infant , Infant, Newborn , Pregnancy , Prevalence , Real-Time Polymerase Chain Reaction , Viral LoadABSTRACT
Torque teno viruses (TTVs) are small, ubiquitous, viruses with a highly diverse, single-stranded, negative sense DNA genome and wide host range. They are detected at high rates in both healthy and diseased individuals and are considered a significant part of the mammalian virome. Similar to human TTVs, swine TTVs (TTSuVs) are epidemiologically linked to several coinfections including porcine circovirus types 2 and 3 and the porcine reproductive and respiratory disease syndrome virus. Experimental infection of gnotobiotic pigs with TTSuVs resulted in lesions in multiple organs and exacerbation of coinfections, making TTSuVs the only members of the Anelloviridae family with experimental evidence for pathogenicity. However, due to the lack of reliable cell culture and animal models, mechanistic studies on viral immunity and pathogenesis are limited. The objective of this review is to summarize the current status of knowledge regarding the biology, detection, pathogenesis and public health significance of TTSuVs, while identifying gaps in knowledge which limit the field.
Subject(s)
DNA Virus Infections/virology , Swine Diseases/virology , Torque teno virus , Animals , Host Specificity , Humans , Swine , Torque teno virus/classification , Torque teno virus/physiologyABSTRACT
BACKGROUND: Assessment of the intensity of immunosuppression in transplant recipients to estimate the risk of rejection and infection is not entirely satisfactory at the present time. Determination of Torque teno virus (TTV) viral load appears to be a promising tool in this setting. OBJECTIVES: We evaluated the level of replication and kinetics of TTV during the first three months after kidney transplantation compared to BK virus replication. RESULTS: In a retrospective cohort of 116 renal transplant recipients, TTV viral load gradually increased during the first three months post-transplantation with no significant difference or discriminatory threshold between patients with and without BK virus replication. However, the level of TTV replication appeared to be indirectly related to the risk of BK virus replication, particularly according to the induction treatment used (antithymocyte globulin: ATG or basiliximab). Among patients receiving ATG, those receiving cyclosporine had significantly lower TTV viral loads (p < 0.01) with threefold lower reactivation of BKPyV (13 vs 37%) 3 months post-transplantation. Similarly, among the women in our cohort, TTV viral load was significantly higher in women receiving ATG (6.58 ± 1.57 versus 4.62 ± 2.0 log10 copies/mL for basiliximab: p < 0.01), also with threefold higher BKPyV reactivation frequencies (40 vs 13,3%). CONCLUSION: The multiparametric variation of TTV viral load does not appear to be individually appropriate for the early detection or monitoring of possible post-transplant BKPyV virus reactivation in renal transplant recipients.
Subject(s)
BK Virus/physiology , Kidney Transplantation/adverse effects , Torque teno virus/physiology , Adult , BK Virus/drug effects , BK Virus/genetics , Biomarkers/blood , DNA, Viral/blood , Female , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Risk Factors , Torque teno virus/drug effects , Torque teno virus/genetics , Viral Load/drug effects , Virus Replication/drug effectsABSTRACT
Kawasaki disease (KD), first identified in 1967, is a pediatric vasculitis of unknown etiology that has an increasing incidence in Japan and many other countries. KD can cause coronary artery aneurysms. Its epidemiological characteristics, such as seasonality and clinical picture of acute systemic inflammation with prodromal intestinal/respiratory symptoms, suggest an infectious etiology for KD. Interestingly, multiple host genotypes have been identified as predisposing factors for KD. To explore experimental methodology for identifying etiological agent(s) for KD and to optimize epidemiological study design (particularly the sample size) for future studies, we conducted a pilot study. For a 1-year period, we prospectively enrolled 11 patients with KD. To each KD patient, we assigned two control individuals (one with diarrhea and the other with respiratory infections), matched for age, sex, and season of diagnosis. During the acute phase of disease, we collected peripheral blood, nasopharyngeal aspirate, and feces. We also determined genotypes, to identify those that confer susceptibility to KD. There was no statistically significant difference in the frequency of the risk genotypes between KD patients and control subjects. We also used unbiased metagenomic sequencing to analyze these samples. Metagenomic sequencing and PCR detected torque teno virus 7 (TTV7) in two patients with KD (18%), but not in control subjects (P = 0.111). Sanger sequencing revealed that the TTV7 found in the two KD patients contained almost identical variants in nucleotide and identical changes in resulting amino acid, relative to the reference sequence. Additionally, we estimated the sample size that would be required to demonstrate a statistical correlation between TTV7 and KD. Future larger scale studies with carefully optimized metagenomic sequencing experiments and adequate sample size are warranted to further examine the association between KD and potential pathogens, including TTV7.
Subject(s)
DNA Virus Infections/complications , DNA Virus Infections/virology , Mucocutaneous Lymph Node Syndrome/etiology , Torque teno virus/physiology , Alleles , Biomarkers , Child, Preschool , Disease Susceptibility , Evolution, Molecular , Female , Genome, Viral , Genomics/methods , Genotype , Humans , Infant , Male , Metagenome , Metagenomics , Odds Ratio , SeasonsABSTRACT
Monitoring the human virome has been recently suggested as a promising and novel area of research for identifying new biomarkers which would help physicians in the management of transplant patients. Imbalance of the immune system in transplant recipients has a significant impact on replication of Torquetenovirus (TTV), the most representative and abundant virus of human virome. TTV kinetic was studied by real-time PCR in 280 liver or kidney transplant recipients who underwent different drug regimens to maintain immunosuppression. During one-year post-transplant follow-up, TTV viremia fluctuated irrespective of transplanted organ type but consistent with the immunosuppression regimen. TTV kinetic in patients who manifested cytomegalovirus (CMV) reactivation within the first four months post-transplant differed from that observed in patients who did not experience CMV complications. Importantly, plasma TTV load measured between day 0 and 10 post-transplant was significantly higher in CMV DNA positive than in CMV DNA negative patients. TTV viremia above 3.45 log DNA copies/ml within the first 10 days post-transplant correlates with higher propensity to CMV reactivation following transplantation. This study provides further evidence for using early post-transplant TTV viremia to predict CMV reactivation in liver or kidney transplant recipients.
Subject(s)
Cytomegalovirus Infections/virology , Cytomegalovirus/physiology , Kidney Transplantation , Postoperative Complications/virology , Torque teno virus/physiology , Adult , Aged , Aged, 80 and over , Cytomegalovirus Infections/diagnosis , Female , Humans , Immunosuppression Therapy , Male , Middle Aged , Postoperative Complications/diagnosis , Prognosis , Time Factors , Transplant Recipients , Viral Load , Viremia , Virus Activation , Young AdultABSTRACT
PURPOSE: Renal impairment is a common complication after liver transplantation (LT). While BK polyomavirus (BKV) has been linked to renal failure in kidney transplant recipients, Torque teno virus (TTV) is a surrogate marker for immunosuppression that does not have a clear association with any human disease. The impact of BKV and TTV on renal impairment after LT is unknown. METHODOLOGY: In this retrospective study, urine and serum samples from 136 liver transplant recipients were screened for BKV and TTV by quantitative PCR. In addition, serum was screened for BKV-specific antibodies and the VP1 typing region was sequenced for BKV genotyping. All parameters were correlated with clinical data.Results/Key findings. BK viruria was detected up to 21 years after transplantation in 16.9â% of cases. BK viraemia was detected in 8.7â% of patients with BK viruria up to 4 years after LT. BKV-specific antibodies were detected in 93.6â% of all LT recipients and correlated with BKV viral load in urine. There was no correlation between renal impairment and the detection of BK DNA in urine (OR 0.983). TTV DNA was detected in 84.6â% of serum samples and in 66.6â% of urine samples. The TTV viral load in serum correlated with the BKV viral load but had no impact on renal impairment. CONCLUSION: Our data indicate that the detection of BKV and TTV is not a risk factor for renal impairment after LT. A correlation of TTV and BKV viral load seems to be an indicator for the immune status of the host.
Subject(s)
BK Virus/physiology , DNA Virus Infections/virology , Liver Diseases/surgery , Liver Transplantation/adverse effects , Polyomavirus Infections/virology , Renal Insufficiency, Chronic/virology , Torque teno virus/physiology , Adult , Aged , BK Virus/genetics , BK Virus/isolation & purification , DNA Virus Infections/etiology , DNA Virus Infections/physiopathology , Female , Humans , Male , Middle Aged , Polyomavirus Infections/etiology , Polyomavirus Infections/physiopathology , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Torque teno virus/genetics , Torque teno virus/isolation & purification , Transplant Recipients/statistics & numerical data , Viral Load , Virus Replication , Young AdultABSTRACT
INTRODUCTION: Zinc plays an important role in thymic function and immune homeostasis. We performed a prospective clinical trial using a high-dose zinc oral supplementation to improve the immune reconstitution after hematopoietic stem cell transplant (HSCT). PATIENTS AND METHODS: We enrolled 18 patients undergoing autologous HSCT for multiple myeloma. Nine patients were randomized to receive only a standard antimicrobial prophylaxis; whereas, nine patients received in addition 150â¯mg/day of zinc from day +5 to day +100 after transplant. RESULTS: CD4+ naïve lymphocytes and TRECs showed a significant increase from day +30 until day +100 only in the zinc-treated group. Moreover, the load of Torquetenovirus, a harmless virus that replicates in course of immunedepression, increased at day +100 only in the control group. No severe adverse events were reported during the zinc consumption. CONCLUSION: First data from the ZENITH trial suggest that high-dose zinc supplementation is safe and may enhance the thymic reconstitution after HSCT. Registered: http://Clinicaltrials.gov (NCT03159845); and EUDRACT: 2014-28 004499-47.
Subject(s)
CD4-Positive T-Lymphocytes/metabolism , DNA Virus Infections/etiology , Dietary Supplements , Receptors, Antigen, T-Cell/metabolism , Stem Cell Transplantation/adverse effects , Torque teno virus/physiology , Virus Activation , Zinc/administration & dosage , Aged , CD4-Positive T-Lymphocytes/immunology , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Male , Middle Aged , Transplantation, Autologous , Transplantation, Homologous , Virus Activation/drug effects , Virus Activation/immunologyABSTRACT
BACKGROUND: Torque teno virus is a small chronically persisting circular negative ssDNA virus reaching near 100% prevalence. It is reported to be a marker for immune function in immunocompromised patients. The possibility of vertical maternal-fetal transmission remains controversial but incidence rate of TTV DNA in children increased with age. TTV dynamics well studied for allogeneic hematopoietic stem cell transplantation as a predictor of post-transplant complications but there is no viral proliferation kinetics data for other patient groups or healthy individuals. The aim of this study was to determine TTV dynamics during the first year of life of healthy infants. METHODS: Ninety eight clinically healthy breastfeeding infants (1-12 months of age) were analyzed by quantitative PCR for the whole blood TTV load with the test sensitivity of about 1000 viral copies per milliliter of blood (total number of samples including repeatedly tested infants was 109). RESULTS: 67% of all analyzed samples were TTV-positive demonstrating significant positive correlation between age and TTV load (r = 0.81, p < 0.01). CONCLUSIONS: This is the first study to suggest that viral load increases during the first year of life reaching a plateau after 6 months with strong proliferation for the first 60 days. Our data well correlates with TTV dynamics in patients following allogeneic hematopoietic stem cell transplantation.
Subject(s)
DNA Virus Infections/virology , Torque teno virus/physiology , Age Factors , DNA Virus Infections/blood , DNA Virus Infections/genetics , DNA, Viral/genetics , Female , Humans , Infant , Male , Prevalence , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Viral LoadABSTRACT
Torque teno viruses [TTVs] are negative sense, single-stranded, DNA viruses, which are distributed globally in several mammalian hosts such as humans, apes, sheep and swine in a species-specific manner. While the pathogenic potential of TTVs is under debate, recent experimental studies in gnotobiotic pigs indicate that swine TTVs, TTSuV1 in particular, can act as a primary or co-infecting pathogen. Hence, determining whether TTSuV1 can infect other mammals would eventually further our understanding of viral pathogenesis, especially in coinfections. In this study, we tested sera from horses, cattle, sheep, dogs and elk for the presence of TTSuV1 DNA using a panel of TTSuV1-specific primers, and assessed the extent of sero-conversion to TTSuV1 in the selected species. We found that TTSuV1 DNA was detected in 46.7% of equines, 70% of canine, 100% of bovine, 40% of ovine and 93.3% of elk samples. However, significant TTSuV1 specific antibody responses were detected only in the bovine, ovine and equine samples but not the canine or elk samples, indicating that these animals could support the replication of TTSuV1. This combined serological and molecular epidemiological profile of TTSuV1 infection in five different species indicates the host range of species-specific TTVs could be wider than initially believed. Further studies are required to understand the health risks to these animal species from TTSuV-1 infection.
Subject(s)
DNA Virus Infections/veterinary , Torque teno virus/physiology , Animals , DNA Virus Infections/transmission , DNA, Viral/blood , Host Specificity , Mammals/virology , Molecular Epidemiology , Seroepidemiologic StudiesABSTRACT
Torquetenovirus (TTV) has been proposed as a marker of immune function in patients receiving immunosuppression after solid organ transplantation. This study aimed to define TTV plasma dynamics and investigate clinical associations in patients following allogeneic hematopoietic stem cell transplantation (HSCT). This was a single-center prospective longitudinal study involving 50 consecutive patients treated with HSCT between March 2015 and April 2016. TTV plasma DNA levels were measured with quantitative PCR at 12 consecutive time points during the first year after HSCT. Forty of the 50 patients (80%) had detectable TTV viremia before HSCT (median level, 5.37 log10 copies/mL; interquartile range [IQR], 3.51-6.44 log10 copies/mL). All patients subsequently developed TTV viremia during the follow-up period. Plasma viral loads evolved dynamically over time, with a peak of 8.32 log10 copies/mL (IQR, 7.33-9.35 log10 copies/mL) occurring at 79 days (IQR, 50-117 days) following HSCT and a stable plateau toward the end of the follow-up period. The type of malignancy, the use of antithymocyte globulin during conditioning, and the occurrence of acute graft-versus-host disease requiring systemic therapy had temporary effects on TTV dynamics. TTV levels showed a significant correlation with absolute lymphocyte counts following engraftment (rs = -.27; P < .01) and with cytomegalovirus (CMV; rs=.39; P < .01) and Epstein-Barr virus (EBV; rs=.45; P = .02) viral loads during phases of viremia. Immune-related clinical events were not predicted by TTV levels. TTV viremia occurred universally and was sustained throughout the first year after HSCT. Several variables and events before and after HSCT were correlated with TTV levels and hint toward immune marker properties of TTV, but their complex interactions might perturb the capability of TTV to predict immune-related complications in this population.
Subject(s)
Biomarkers/analysis , Hematopoietic Stem Cell Transplantation/adverse effects , Torque teno virus/physiology , Adult , Biomarkers/blood , Cytomegalovirus , DNA Virus Infections/blood , DNA Virus Infections/immunology , DNA, Viral/blood , Female , Herpesvirus 4, Human , Humans , Longitudinal Studies , Lymphocyte Count , Male , Prospective Studies , Transplantation, Homologous/adverse effects , Viral LoadABSTRACT
OBJECTIVES: Because torque teno virus (TTV) has been implicated in tumorigenesis as a cocarcinogen, we studied TTV prevalence in saliva and biopsy samples from head and neck cancer (HNCC) patients, patients with premalignant lesions of oral cancer, and controls. We also wished to determine the TTV genotypes in HNCC patients. METHODS: A seminested polymerase chain reaction (PCR) amplifying the N22 region of the TTV genome, as well as direct sequencing of PCR fragments, was used. RESULTS: TTV prevalence was higher in HNCC patients (saliva: 27/71, 38%; tumor biopsy: 22/74, 30%) than in controls (saliva: 8/56, 14%; oral mucosa: 1/19, 5%). TTV prevalence was also high in patients with premalignant lesions of oral carcinoma (saliva: 9/18, 50%; biopsy: 5/21, 24%). By phylogenetic analysis, TTV belonging mostly to genotypes 1 and 2 was found in HNCC patients. In most of the cases, identical TTV strains were present in the biopsy and salivary sample of the same HNCC patient. In addition, the same TTV strain was detected in 2 laryngeal carcinoma biopsies obtained from 2 independent patients. CONCLUSIONS: Our data are compatible with the idea that TTV might act as a cocarcinogen in certain cases of HNCC. Alternatively, HNCC may facilitate either TTV replication or TTV entry into the saliva.
Subject(s)
DNA Virus Infections/epidemiology , Head and Neck Neoplasms/virology , Saliva/virology , Torque teno virus/genetics , Torque teno virus/isolation & purification , Adult , Biopsy , DNA Virus Infections/diagnosis , DNA, Viral , Female , Genome, Viral , Genotype , Humans , Laryngeal Neoplasms/virology , Male , Middle Aged , Mouth Neoplasms/virology , Phylogeny , Polymerase Chain Reaction , Prevalence , Salivary Glands/pathology , Salivary Glands/virology , Torque teno virus/classification , Torque teno virus/physiologyABSTRACT
BACKGROUND: The human Torque Teno virus (TTV) causes persistent viremia in most immunocompetent individuals. Elevated TTV levels are observed after solid organ transplantation and are related to the extent of immunosuppression especially during the phase of maintenance immunosuppression. However, the extent to which the TTV increase in the early phase post-transplantation is associated with the patient's immunosuppressive state is unclear. OBJECTIVES: In this study, we assessed the TTV increase dynamics in detail during the first three months after lung transplantation under a defined immunosuppressive regimen and in relation to the pre-transplant TTV level. STUDY DESIGN: Forty-six lung transplant recipients (LTRs) were included in this prospective longitudinal study. All received alemtuzumab induction combined with tacrolimus and corticosteroids immunosuppressive therapy. Plasma TTV DNA was monitored before transplantation and regularly within the first three months post-transplantation (n = 320 samples; mean sampling interval: 12.2 days). RESULTS: In 43/46 LTRs (93%), TTV DNA was detectable before transplantation (median 4.4 log10 copies/mL; range: 2.0-6.4). All 46 LTRs showed a TTV increase post-transplantation, which followed a sigmoidal-shaped curve before the median peak level of 9.4 log10 copies/mL (range: 7.6-10.7) was reached at a median of day 67 (range: 41-92). The individual TTV DNA doubling times (range: 1.4-20.1 days) significantly correlated with the pre-transplant TTV levels calculated over 30 or 60 days post-transplantation (r = 0.61, 0.54, respectively; both P < 0.001), but did not correlate with the mean tacrolimus blood levels. Pre-transplant TTV levels were not associated with time and level of the patients' post-transplant TTV peak load. CONCLUSION: The TTV level may be used to mirror the state of immunosuppression only after the patients' initial peak TTV level is reached.
Subject(s)
Lung Transplantation/adverse effects , Plasma/virology , Torque teno virus/physiology , Viral Load , Adult , Aged , Female , Humans , Immunosuppression Therapy/adverse effects , Kinetics , Male , Middle Aged , Plasma/drug effects , Viral Load/drug effects , Young AdultABSTRACT
Torque teno viruses (TTV) are widespread in humans, swine as well as in several other animal species. In market ready swine, the reported prevalence ranges between 11% and 100%. Through a national retail sampling plan from the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) program, 283 and 599 liver and pork chop samples, respectively, were collected over a 12-month period from commercial establishments in 5 selected geographical regions of Canada to assess the presence of Torque teno sus viruses (TTSuVs) in these products. TTSuVs were detected in 97.9% of pork chops with viral loads ranging between 1×10(4) and 9.9×10(5) genomic copies (gc)/g and 98.6% of liver samples with viral loads ranging from 1×10(5) to 9.9×10(6) gc/g. A selection of 20 positive samples (10 pork chop and 10 liver) from the 5 geographical regions were further tested for the production, of a 305bp fragment for TTSuV1 and a 253bp fragment for TTSuV2 in the non-coding region. TTSuV1 was present in all 10 liver and 10 pork chops samples while TTSuV2 was detected in 10 liver and 9 pork chop samples. Two different TTSuV1 sequences were simultaneously detected from 5 of 20 samples and 2 different TTSuV2 sequences were detected from 6 of 19 samples. The omnipresence of TTSuVs in commercial pork samples may allow its use as a viral indicator to monitor the effectiveness of cleaning and disinfecting process in slaughtering, cutting, slicing and packaging facilities.
Subject(s)
Liver/virology , Meat/virology , Torque teno virus/classification , Torque teno virus/physiology , Viral Load , Animals , Canada , Genes, Viral/genetics , Phylogeny , Prevalence , Swine , Torque teno virus/genetics , Torque teno virus/isolation & purificationABSTRACT
The expression profiles of nonstructural proteins (NSPs) in Torque teno sus virus 2 (TTSuV2) have not yet been characterized. Here, we determined the coding sequences of the TTSuV2 NSPs ORF2, ORF2/2, and ORF2/2/3 by overlapping polymerase chain reaction (PCR) and subsequent expression in bacterial and mammalian cells. We generated two monoclonal antibodies (mAbs), 2E5 and 6F8, from mice immunized with mixed Escherichia coli expressing His-tagged ORF2 and ORF2/2. Enzyme-linked immunosorbent assay (ELISA) and western blot analysis revealed that, 2E5 mAbs bound to the consensus sequences of ORF2, ORF2/2, and ORF2/2/3, while 6F8 recognized the common sequences of ORF2/2 and ORF2/2/3. Immunofluorescence assay (IFA) revealed that ORF2 was localized in the cytoplasm, ORF2/2, in the nucleus but not the nucleolus, and ORF2/2/3, in the peri-nuclear region. To identify the expression profiles of TTSuV NSPs, a circular TTSuV2_ZJ (GenBank: KF660540) genomic DNA clone was constructed and transfected into HEK293T and HeLa cells. Splicing mRNAs and the expression and localization of ORF2/2 and ORF2/2/3 were identified by RT-PCR, western blot analysis, and IFA, respectively. However, ORF2 was not detected either at the RNA or protein level. Our study is the first to provide experimental evidence of the existence of ORF2/2 and ORF2/2/3 at the protein level. Moreover, the mAbs have potential applications in future research on TTSuV2 viral protein function and diagnosis of related diseases.
Subject(s)
Torque teno virus/genetics , Viral Nonstructural Proteins/genetics , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Blotting, Western , Cell Line , Enzyme-Linked Immunosorbent Assay , Female , Humans , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Sequence Analysis, DNA , Torque teno virus/physiology , Virus ReplicationABSTRACT
In this study we detail the detection and genetic analysis of a novel porcine boca-like virus (PBo-likeV) in archival sera and tissue samples from pigs from farms in Great Britain. We also investigate the distribution of porcine circovirus type 2 (PCV2) genotypes and Torque teno sus virus (TTSuV) genogroups 1 and 2 in combination with this novel PBo-likeV. PBo-likeV was detected in over 70% of all tissues investigated. Over 24% of all tissues recovered from PMWS-affected animals had all viruses present and 25% of tissues recovered from non-PMWS-affected pigs were positive for all 4 viruses.
Subject(s)
DNA Virus Infections/veterinary , DNA Viruses/physiology , Swine Diseases/epidemiology , Swine Diseases/virology , Animals , Bocavirus/classification , Bocavirus/genetics , Bocavirus/physiology , Circovirus/classification , Circovirus/genetics , Circovirus/physiology , DNA Virus Infections/epidemiology , DNA Virus Infections/virology , DNA Viruses/classification , DNA Viruses/genetics , DNA, Viral/genetics , Genotype , Molecular Sequence Data , Phylogeny , Swine , Torque teno virus/classification , Torque teno virus/genetics , Torque teno virus/physiology , United Kingdom/epidemiology , Viral Core Proteins/geneticsABSTRACT
Chronic hepatitis B and C virus infections are universally accepted as causes of hepatocellular carcinoma in humans. Hepatitis A and E viruses cause only acute self-limiting infections of the liver. Of the remaining hepatitis viruses - Delta hepatitis, hepatitis G (GB-C), TT and SEN - all have at some time been incriminated as causes of hepatocellular carcinoma. Delta hepatitis virus requires helper functions from hepatitis B virus to become invasive. Chronic Delta/hepatitis B viral co-infection runs a more severe course than that resulting from chronic hepatitis B virus infection alone, with progression to cirrhosis being more likely and more rapid. A substantial majority of the early studies did not find an increased incidence of hepatocellular carcinoma in co-infected individuals. But more recently, an increased incidence of the tumour has been recorded more often than no increase. Further studies are needed to draw a firm conclusion with regard to the hepatocarcinogenic effect of dual Delta/hepatitis B virus co-infection. With one exception, no published study (of 13) has incriminated chronic infection with hepatitis G virus as a cause of hepatocellular carcinoma. The dissenting study, published in 1999, was the only one performed in the United States. Fewer studies of the hepatocarcinogenic effect of TT virus have been performed. Apart from one study, published in 1999, no convincing evidence is available that supports a causal role for TT virus in hepatocarcinogenesis. The exception was in Japanese patients with high hepatitis C viral loads but independent of chronic hepatitis C virus infection. No evidence has been produced to indicate that SEN virus causes hepatocellular carcinoma.