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Background: Nonpathogenic torque teno viruses (TTVs) are highly prevalent in transplant recipients and associated with immunosuppression. Studies in kidney transplant patients have proposed assessment of TTV load for risk stratification of clinically overt graft rejection. The value of TTV quantification in the context of subclinical rejection has not been evaluated., Methods: In this prospective trial, 307 consecutive kidney transplant recipients were subjected to per-protocol monitoring of plasma TTV. TTV was analyzed in the context of protocol biopsies (n = 82), scheduled 1 year posttransplantation., Results: TTV load at the time of biopsy was lower in recipients with rejection (n = 19; according to Banff, including borderline changes suspicious for acute T cell-mediated rejection) than those without rejection (n = 63) whereby each log increase in TTV copies/mL decreased the risk for rejection by 9% (risk ratio 0.91, 95% confidence interval, 0.85-0.97; P = 0.004). Development of chronic lesions (cg, cv, ci, ct, ah, ptcml) was associated with the number of days with a TTV load <1 × 106 copies/mL between months 3 and 12 posttransplant (β 0.07, 95% confidence interval, 0.01-0.14; P = 0.02)., Conclusions: This trial demonstrates an association between TTV and subclinical graft rejection in kidney transplant recipients. A TTV load <1 × 106 copies/mL suggests suboptimal immunosuppression., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown. To determine the impact of ocular enucleation and prosthesis placement on the ocular surface microbiome, we sampled conjunctival swabs from 20 anophthalmic and 20 fellow-eye intact conjunctiva. DNA was extracted and subjected to quantitative 16S rDNA PCR, biome representational karyotyping (BRiSK), and quantitative PCR (qPCR) confirmation of specific organisms. 16S ribosomal qPCR revealed equivalent bacterial loads between conditions. Biome representational in silico karyotyping (BRiSK) demonstrated comparable bacterial fauna between anophthalmic and intact conjunctiva. Both torque teno virus and Merkel cell polyoma virus (MCPyV) were detected frequently in healthy and anophthalmic conjunctiva. By qPCR, MCPyV was detected in 19/20 anophthalmic samples compared with 5/20 fellow eyes. MCPyV copy number averaged 891 copies/ng in anophthalmic conjunctiva compared with 193 copies/ng in fellow eyes (p < 0.001). These results suggest that enucleation and prosthesis placement affect the ocular surface flora, particularly for the resident virome. As MCPyV has been shown to be the etiologic cause of Merkel cell carcinoma, understanding the mechanisms by which the ocular surface regulates this virus may have clinical importance., (© 2021. The Author(s).)

Introduction: Estimation of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transfusion risk in blood donors is essential for monitoring the safety of the blood supply and the impact of new screening tests. Due to improvements in donor selection and continuing progress in screening assays, residual risk of virus transmission has significantly decreased over the past years. It is not practical and sometimes even not possible to measure residual risk in blood donors directly and mathematical models are used. The aim of this study was to calculate the prevalence, incidence rates of HBV, HCV and HIV infections and analyse evolution of their transmission residual risk from 2004 to 2018 at the National Blood Center of Lithuania., Materials and Methods: Data from the archives of the National Blood Center of Lithuania from 2004 to 2018 was retrospectively analysed. The residual risk was calculated for each virus and year by applying the incidence/window-period model suggested by World Health Organization. For the analysis of the residual risk yearly trends a linear regression was used., Results: A total of 754,755 blood donors and 1,245,568 donations were included in the analysis and represented a 2.06 donations per donor over 15 years. Average residual risk for HBV, HCV and HIV respectively was 570.04, 807.14 and 35.72 per 1,00,000 donations. During the study period, there was statistically significant downward trend in the residual risk for every analysed virus., Discussion: Residual risk of virus transmission has been steadily decreasing over past 15 years in Lithuanian donors, but the current risk remains quite high. It is difficult to establish how much the risk is affected by statistical assumptions or virus prevalence in general population. However, results of this study indicate the need of the population screening program of transfusion transmitted viruses., Competing Interests: The authors have declared that no competing interests exist.

The review presents the data accumulated for more than 20 years of research of torque teno virus (TTV). Its molecular genetic structure, immunobiology, epidemiology, diagnostic methods, possible replication sites, and pathogenicity factors are described. TTV is a virus that is frequently detectable in patients with different viral hepatitides, in cases of hepatitis without an obvious viral agent, as well as in a healthy population. There is evidence suggesting that biochemical and histological changes occur in liver tissue and bile duct epithelium in TTV monoinfection. There are sufficient histological signs of liver damage, which confirm that the virus can undergo a replicative cycle in hepatocytes. Along with this, cytological hybridization in TTV-infected cells has shown no substantial cytopathic (cell-damaging) effects that are characteristic of pathogenic hepatotropic viruses. Studying TTV has led to the evolution of views on its role in the development of human pathology. The first ideas about the hepatotropism of the virus were gradually reformed as new data became available on the prevalence of the virus and its co-infection with other viruses, including the viruses of the known types of hepatitides. The high prevalence of TTV in the human population indicates its persistence in the body as a virome and a non-pathogenic virus. It has recently been proposed that the level of TTV DNA in the blood of patients undergoing organ transplantation should be used as an endogenous marker of the body's immune status. The available data show the polytropism of the virus and deny the fact that TTV can be assigned exclusively to hepatitis viruses. Fortunately, the rare detection of the damaging effect of TTV on hepatic and bile duct epithelial cells may be indirect evidence of its conditionally pathogenic properties. The ubiquity of the virus and the variability of its existence in humans cannot put an end to its study., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Due to the high number of transfusions which patients with hereditary hemoglobinopathies (thalassemia, sickle cell disease) receive, they represent high risk of acquiring parenterally transmitted infectious diseases. In this respect, non pathogenic human commensal viruses, which also demonstrate parenteral transmission routes might also be acquired. One of the most widely spread parenterally-transmitted human commensal viruses include the Human Pegivirus-1 (HPgV-1, GBV-C) and Torque teno viruses (TTV) including its SEN virus-like (SENV) forms. The objective of this study was to evaluate the prevalence of HPgV-1 RNA and SENV-like viruses, among a group of patients with beta-thalassemia from a Blood Transfusion Center in the São Paulo State, Brazil. The prevalence of HPgV-1 RNA was 14.3 % (n = 6/42) and all of the positive samples were characterized as belonging to genotype 2 (83.3 % were referred to subgenotype 2A and 16.7 % to 2B). The prevalence of SENV-like viruses was 28.6 % (n = 12/42). SENV-like viruses of the genotypes SENV-H and SENV-A were classified during the performed phylogenetic analysis. Our study came as a continuation of a viral metagenomic survey among multiple transfused patients with beta-thalassemia. The obtained results shed a light on the prevalence and genotype distribution of commensal parenterally transmitted viruses like HPgV-1 and SENV in this specific population. However, more studies are needed to evaluate the clinical impact of these apparently non-pathogenic viruses in patients with thalassemia and their significance for the hemotherapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Torque teno virus (TTV) is an unenveloped, circular, single stranded DNA virus with a genome size of approximately 3.8 kb. Previous studies have demonstrated varying grades of association between TTV DNA levels and immune deficiencies related to age, chronic infections and cancer. Alzheimer's disease (AD) has been related to persistent viral infections such as HSV-1 and CMV, but it is not known whether TTV viral load could serve as a functional biomarker of cellular immunity in this setting. Therefore, the objective of this study was to investigate whether TTV infection and viral load is related to AD status, CMV immunity, systemic inflammation or HLA types connected to anti-viral immunity. A total of 50 AD subjects and 51 non-demented controls were included in the study. AD subjects were diagnosed according to NINCDS-ADRDA and DSM-IV criteria and neuroradiologic findings were consistent with the diagnosis. TTV viral load was analyzed in plasma samples using a quantitative real-time PCR. Using a cut-off for TTV status at 200 copies/ml, 88% (89/101) of the study subjects were classified as TTV positive. TTV viral load significantly increased with age (beta 0.049 per year, p<0.001) but significantly decreased in relation to CMV IgG levels (beta -0.022 per 1000 units, p = 0.005) and HLA-B27 positivity (beta -0.53, p = 0.023). In conclusion, TTV immune control is not significantly affected by AD status, but appears related to age, CMV humoral immune response and HLA type., Competing Interests: The authors have declared that no competing interests exist.

Human anelloviruses (Torque Teno Virus (TTV) and TTV Like Mini Virus (TLMV)) are now being reported at a high prevalence across the world, with a controversial disease-inducing potential. The aim of this study was to investigate the role of these anellovirus in vitreous of patients with presumed infectious endophthalmitis. After informed consent, vitreous fluid from patients with endophthalmitis (n = 103) and non-infectious pathologies (n = 102) were analyzed for the presence of TTV and TLMV DNA by qPCR with the limit of quantification defined as 100 copies per reaction. Among the patients clinically diagnosed with endophthalmitis, 29 of the 40 culture proven samples (72.5%) and 42 out of 63 (66.6%) of culture-negative samples were positive for presence of TTV/TLMV. Interestingly, 51 of the 102 (50%) samples in the control group were also positive for TTV/TLMV. Comparing the clinical outcome among patients diagnosed with endophthalmitis, we observed no significant association in the final visual acuity of patients who were positive for presence of TTV/TLMV, however, these patients had significantly higher repeat antibiotic injections (p = 0.03). Further evidence is however needed to correlate TTV / TLMV with a particular pathology or group of pathologies in the eye., Competing Interests: The authors have declared that no competing interests exist.

The torque teno sus virus (TTSuV) is an emerging virus threating the Suidae species of unclear pathogenicity, although it was previously reported as a worsening factor of other porcine diseases, in particular, porcine circovirus associated disease (PCVAD). Here, a comprehensive codon usage analysis of the open reading frame 1 (ORF1), which encodes the viral capsid protein, was undertaken for the first time to reveal its evolutionary history. We revealed independent phylogenetic processes for the two genera during TTSuV evolution, which was confirmed by principal component analysis (PCA). A low codon usage bias was observed in different genera and different species, with Kappatorquevirus a (TTSuVk2a) displaying the highest, which was mainly driven by mutation pressure and natural selection, especially natural selection. Overall, ATs were more abundant than GCs, along with more A-ended synonymous codons in relative synonymous codon usage (RSCU) analysis. To further confirm the role of natural selection and TTSuV adaptation to the Suidae species, codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses were performed, which showed different adaptations for different TTSuVs. Importantly, we identified a more dominant role of Sus scrofa in the evolution of Iotatorquevirus (TTSuV1), with the highest CAI values and lowest RCDI values compared to Sus scrofa domestica . However, in TTSuVk2, the roles of Sus scrofa and Sus scrofa domestica were the same, regarding codon usage, with similar CAI and RCDI values. Our study provides a new perspective of the evolution of TTSuV and valuable information to develop control measures against TTSuV.

Background: Drug-induced immunosuppression in kidney transplant recipients is crucial to prevent allograft rejection, but increases risk for infectious disease. Immunologic monitoring to tailor immunosuppressive drugs might prevent alloreactivity and adverse effects simultaneously. The apathogenic torque teno virus (TTV) reflects the immunocompetence of its host and might act as a potential candidate for a holistic monitoring., Methods: We screened all 1010 consecutive patients from the prospective Vienna Kidney Transplant Cohort Study for availability of allograft biopsies and adequately stored sera for TTV quantification by polymerase chain reaction., Results: Patients with acute biopsy-proven alloreactivity according to the Banff classification (n = 33) showed lower levels of TTV in the peripheral blood compared to patients without rejection (n = 80) at a median of 43 days before the biopsy. The risk for alloreactivity decreased by 10% per log level of TTV copies/mL (risk ratio, .90 [95% confidence interval, .84-.97]; P = .005). TTV levels >1 × 106 copies/mL exclude rejection with a sensitivity of 94%. Multivariable generalized linear modeling suggests an independent association between TTV level and alloreactivity., Conclusions: TTV is a prospective biomarker for risk stratification of acute biopsy-proven alloreactivity in kidney transplant recipients and might be a potential tool to tailor immunosuppressive drug therapy., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Multiple sclerosis (MS) causes demyelination of white matter of central nervous system and neuro-degeneration due to inflammation. Different types of MS, as well as disease progression, come with different pathology and pathophysiology. The objective of this study was to evaluate the possible association between different micro-organisms and the relapse or progression of MS. Studies indexed in Medline/PMC, Scopus and Web of Science published without time and language limitation until March 2017 were identified through the search terms "infection" or "infectious" and "multiple sclerosis". A total of 20878 abstracts were identified through the initial search terms. Selection of articles and assessment of their quality was done based on Cochrane library guidelines. Full texts were reviewed for 33 articles out of which 14 articles met the criteria for inclusion. Different micro-organisms are known to play roles in the pathogenesis of MS and its relapse; including Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV), Chlamydia pneumoniae and Torque teno virus (TTV). But in this review only HHV-6, C. pneumoniae and TTV have been considered to play a role in disease progression in some studies and not all of them. This review concluded that some micro-organisms such as HHV-6, C. pneumoniae and TTV have been considered as cofactors to make MS a progressive type. It should be considered that these findings do not necessarily rule out the role of other pathogens in MS progression but may represent population differences or different sensitivity of the technique used.

Monitoring Torque teno virus (TTV) DNA load helps to estimate the risk of opportunistic infections in solid organ transplant recipients. We investigated whether the early kinetic pattern of plasma TTV DNA load after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associates with subsequent CMV and EBV DNAemia. This study included 71 allo-HSCT patients. We found that the area under the curve (AUC) for log 10 TTV DNA loads quantified by days 20 and 30 after transplantation (TTV DNA load AUC 20-30 ), was significantly lower (P=0.036) in patients who subsequently developed CMV DNAemia requiring preemptive antiviral therapy (n=17) than in those who did not (n=8) or had no CMV DNAemia (n=19). Patients displaying TTV DNA load AUC 20-30 ⩽2.8 copies × days × mL -1 were more likely to have high-level CMV DNAemia. A trend towards a direct correlation between TTV DNA AUC 20-30 and CMV-specific interferon-γ CD8+ T-cell counts by day +30 was noted (P=0.095). However, this dynamic parameter was not useful for anticipating the occurrence of either CMV recurrences (n=12) or EBV DNAemia (n=34). In summary, it may be possible to identify a subset of allo-HSCT patients at a high risk of developing high-level CMV DNAemia by analyzing the kinetics of plasma TTV DNA load early after engraftment.

Background: TTV has been detected in almost every human tissue type or body fluid reaching near 100% prevalence. Several studies report mother-to-child postnatal transmission of TTV in infancy but the risk of transplacental transmission of TTV is still unclear., Methods: The blood and plasma collected postpartum from 100 mother-child pairs were analyzed using TTV-specific qPCR. Samples were collected from the peripheral vein of the mother and the umbilical cord., Results: Eighty four percent of pregnant women were TTV positive (median titers: 8 × 10 4 copies/mL; range: 10 3 - 3 × 10 7 ). The TTV load in plasma was approximately 100 times lower than in whole blood. TTV was not detected in any of cord blood samples., Conclusions: Our data demonstrate the lack of transplacental transmission of TTV (or effective prenatal inhibition of viral proliferation). The presence of the virus in infants may be associated with mother-to-child transmission through breast feeding or other routes of transmission.

Background: Antibody-mediated rejection (AMR) represents one of the cardinal causes of late allograft loss after kidney transplantation, and there is great need for noninvasive tools improving early diagnosis of this rejection type. One promising strategy might be the quantification of peripheral blood DNA levels of the highly prevalent and apathogenic Torque Teno virus (TTV), which might mirror the overall level of immunosuppression and thus help determine the risk of alloimmune response., Methods: To assess the association between TTV load in the peripheral blood and AMR, 715 kidney transplant recipients (median, 6.3 years posttransplantation) were subjected to a systematical cross-sectional AMR screening and, in parallel, TTV quantification., Results: Eighty-six of these recipients had donor-specific antibodies and underwent protocol biopsy, AMR-positive patients (n = 46) showed only 25% of the TTV levels measured in patients without AMR (P = 0.003). In a generalized linear model, higher TTV levels were associated with a decreased risk for AMR after adjustment for potential confounders (risk ratio 0.94 per TTV log level; 95% confidence interval 0.90-0.99; P = 0.02)., Conclusions: Future studies will have to clarify whether longitudinal assessment of TTV load might predict AMR risk and help guide the type and intensity of immunosuppression to prevent antibody-mediated graft injury., Competing Interests: The authors declare no conflicts of interest.

While recent findings suggest that swine TTVs (TTSuVs) can act as primary or co-infecting pathogens, very little is known about viral immunity. To determine whether TTSuVs downregulate key host immune responses to facilitate their own survival, a swine macrophage cell line, 3D4/31, was used to over-express recombinant TTSuV1 viral particles or the ORF3 protein. Immune gene expression profiles were assessed by a quantitative PCR panel consisting of 22 immune genes, in cell samples collected at 6, 12, 24 and 48h post-transfection. Despite the upregulation of IFN-β and TLR9, interferon stimulated innate genes and pro-inflammatory genes were not upregulated in virally infected cells. The adaptive immune genes, IL-4 and IL-13, were significantly downregulated at 6h post-transfection. The ORF3 protein did not appear do not have a major immuno-suppressive effect, nor did it stimulate anti-viral immunity. Data from this study warrants further investigation into the mechanisms of TTV related immuno-pathogenesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The pathogenic role of torque teno sus virus (TTSuV) in swine is controversial among different studies. The present study intended to evaluate the potential pathogenicity of TTSuV based on its correlations with the histopathological changes, various common concurrently infected viral pathogens including porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV), as well as changes in the distribution and population of host immunocytes such as B lymphocytes, T lymphocytes, and macrophages by using the superficial inguinal lymph nodes (siLNs) of wasting pigs. A tissue microarray consisting of 270 available siLNs collected from 262 clinically wasting and 8 healthy pigs, respectively, were used for the detection of TTSuV1, TTSuV2, PCV2, PRRSV, and PPV by either in situ hybridization (ISH) or immunohistochemical (IHC) staining, and for the detection of various subsets of immunocytes by IHC staining with monoclonal antibodies to CD3, CD79a, and lysozyme. The slides were then subject to digital scanning followed by a semi-quantitative positive pixel evaluation for further statistical analysis. Although a high prevalence of TTSuV1 and/or TTSuV2 infection was noted in both wasting and healthy pigs, the wasting pigs had a significantly higher intensity in both TTSuV1 and TTSuV2 ISH-positive signals than healthy ones did. In the wasting pigs, a significant positive correlation in the tissue viral load was noted between TTSuV1 and TTSuV2 and between TTSuV2 and PCV2, but not between TTSuV1 and PCV2. Conversely, a significant negative correlation in the tissue viral load was revealed between TTSuV2, but not TTSuV1, and PRRSV. The tissue viral load of TTSuV1 was significantly correlated with B cell hyperplasia, while the tissue viral load of TTSuV2 was significantly correlated with increased macrophage population. The ISH positivity of TTSuV2 was significantly correlated with lymphoid depletion and granulomatous inflammation, which are the characteristic histopathological findings in postweaning multisystemic wasting syndrome-affected pigs. These findings suggest that both TTSuV species may have the potential involving the development of porcine circovirus-associated lymphoid lesions via alternating the host immune system., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Teno Torque virus, member of the family of Anelloviridae, has been associated with many autoimmune diseases such as idiopathic hepatitis, systemic lupus erythematosus, and multiple sclerosis. Its viral load tends to be higher in the bone marrow and in tissues with high turnover rate. We report here a case of an 11-month-old infant affected by acute myeloid leukemia who underwent hematopoietic stem cell transplantation, and after 6 months had autoimmune hepatitis and atopic dermatitis. Extremely high-cytokine IP-10 and eotaxin levels were found in her sera, and serological tests and RT-PCR for viruses showed positive results exclusively for Teno Torque virus.

Background and Aim: SEN virus (SENV), is a recently discovered single-stranded DNA virus of Annelloviridae family and is believed may play a role in non A-E hepatitis. We conducted this study to identify the prevalence and clinical association of SENV with acute and chronic hepatitis., Methods: 135 liver disease patients were studied. Extent of liver damage was assessed using the Model for End Stage Liver Disease (MELD) score. A-E viruses and HIV were detected by enzyme immunoassay. Nested PCR was performed for detection of SENV and its genotypes D and H., Results: 34 cases (25.18%) were positive for SEN virus DNA, a statistically significant finding (p < 0.01) of which 22 (64%) had acute viral hepatitis, 4 (11.76%) had chronic viral hepatitis, 3 (8.82%) fulminant hepatic failure and 5 (14.70%) cirrhosis. Mean AST was 47.85 IU/L, ALT 51.2 IU/L and INR 1.73, mean MELD score was 18.38 (11 to 24). 17.64% had severely deranged MELD score. SENV-D genotype was detected in 13 (38%) and SENV-H in 19 (58%) cases. SENV-H occurred in both acute (53%) and chronic hepatitis (47%). SENV-D was strongly associated with acute hepatitis (85%). Cirrhotic and FHF cases were SENV-H positive. 12 (44.11%) were co-infected with HBV, 5 (14.7%) with TTV, 4(11.76%) with HEV, 2 (5.88%) with HCV and 5 (14.4%) with HIV., Conclusion: Significant prevalence of SENV in hepatitis patients was observed. On the basis of clinical findings and abnormal liver function tests, we conclude that SENV appears to be not only hepatotropic but also capable of liver damage. Higher prevalence of SENV-H in cirrhotics may point to its possible role in the development of cirrhosis.

The study describes a novel Torque teno sus virus (TTSuV) species, provisionally named Torque teno sus virus k2b (TTSuVk2b), originally found in commercial pig sera by applying the rolling-circle amplification technique. Full-length sequences of TTSuVk2b were obtained, annotated and used in the phylogenetic analyses, which revealed that TTSuVk2b is a novel Anellovirus species within the genus Kappatorquevirus of the family Anelloviridae. Quantitative PCR techniques were developed to determine total TTSuV DNA quantities as well as the prevalence and viral DNA quantities of TTSuV1, TTSuVk2a and TTSuVk2b. The mean total TTSuV load in seven commercial sera was determined at 6.3 log(10) DNA copies ml(-1) of serum, with TTSuVk2b loads being the lowest at 4.5 log(10) DNA copies ml(-1) of serum. Subsequently, prevalence and loads of TTSuVs were determined in pig sera from 17 countries. TTSuVk2b prevalence ranged from 0 to 100 % with viral loads from 3.3 to 4.6 log(10) copies ml(-1) of sera. TTSuVk2a, so far the only species in the genus Kappatorquevirus, has been linked to an economically important swine disease, namely post-weaning multisystemic wasting syndrome (PMWS). Considering the grouping of TTSuVk2b in the same genus as TTSuVk2a, TTSuVk2b prevalence and viral DNA load were determined in PMWS-affected animals and healthy counterparts. This revealed that TTSuVk2a and TTSuVk2b are not only genetically related, but also that their viral loads in serum are elevated in PMWS animals compared with those of healthy pen mates. In summary, the present work describes a novel TTSuV species including its genetic characterization, epidemiological assessment and potential disease association.

An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections., (Copyright © 2011 UICC.)

The role of swine torque teno sus viruses (TTSuVs) as co-factors in disease syndromes involving porcine circovirus strain 2 (PCV2) and porcine reproductive and respiratory disease syndrome virus (PRRSV) has been a debatable subject. In this study, the prevalence of TTSuVs in Iowa, the leading pork producing state in the U.S., was estimated by a duplex PCR. The PCR is capable of simultaneously detecting both teno sus viruses 1 and 2 (TTSuV1 and 2). Based on an analysis of 300 random samples representing six major geographical regions of the state, the overall prevalence rates for TTSuV1 and 2 were 47.34% and 24.67% respectively while the combined prevalence rate was 52.33%. The epidemiological association of TTSuV1 and 2 with the common etiological agents of the porcine respiratory disease complex (PRDC) namely porcine PRRSV, PCV2, Mycoplasma hyopneumoniae and swine influenza virus (SIV) was estimated in lung tissue derived from 45 pigs showing clinical signs of PRDC. Notably, 86.67% of the PRDC-suspect samples were positive for TTSuV1 in comparison to the baseline population prevalence rate of 47.34%. However, the prevalence of TTSuV2 (26.67%) was not significantly different. TTSuV1 was detected in 80.00%, 81.81%, 75.00% and 77.78% of the PRRSV, SIV, M. hyopneumoniae and PCV2 positive PRDC-suspect samples respectively. Our results indicate that TTSuV1 is strongly associated with clinical PRDC and support the hypothesis that TTSuVs might function as co-factors in PRDC. Further studies to define their possible role in the pathogenesis of swine respiratory diseases are warranted., (Published by Elsevier B.V.)

Multiple sclerosis (MS) is a disease of young adults which is characterized by autoimmune demyelination of the central nervous system. Interaction of genetics and environmental factors are required to cause MS. Among the proposed environmental factors for MS, viral infections are thought to play a role in the pathogenesis of the disease. Torque teno mini virus (TTMV), which has recently been shown to infect humans, is a member of circoviridae, and has a circular DNA with 2860 nucleotides. Since there are a few data about the pathogenicity of this virus, this study sought to investigate the presence of TTMV in sera from MS patients and healthy individuals. We studied 149 serum samples from MS patients and 150 sera of healthy individuals. Serum DNA was extracted using phenol-chloroform and was subjected to nested polymerase chain reaction. TTMV-DNA was detected in 24 (16%) sera of the healthy blood donors and in 21 (14.1%) samples of the MS patients, where the difference did not reach significance (p > .05). The result of this study could not establish an association between TTMV infection and MS.

Genetic and environmental factors jointly determine the susceptibility to develop Multiple Sclerosis (MS). Collaborative efforts during the past years achieved substantial progress in defining the genetic architecture, underlying susceptibility to MS. Similar to other autoimmune diseases, HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are the highest-risk-conferring genes. Less-robust susceptibility effects have been identified for MHC class I alleles and for non-MHC regions. The role of environmental risk factors and their interaction with genetic susceptibility alleles are much less well defined, despite the fact that infections have long been associated with MS development. Current data suggest that infectious triggers are most likely ubiquitous, i.e., highly prevalent in the general population, and that they require a permissive genetic trait which predisposes for MS development. In this review article, we illustrate mechanisms of infection-induced immunopathologies in experimental animal models of autoimmune CNS inflammation, discuss challenges for the translation of these experimental data into human immunology research, and provide future perspectives on how novel model systems could be utilized to better define the role of viral pathogens in MS., (2010 Elsevier B.V. All rights reserved.)

MS is an immune mediated disease of the central nervous system (CNS) characterized by demyelination, axonal damage and neurologic disability. The primary cause of this CNS disease remains elusive. Here we will address our current understanding of the role of viruses as potential environmental triggers for MS. Virus infections can act peripherally (outside the CNS) or within the CNS. The association of viral infections with demyelinating disease, in both animals and humans, will be discussed, as will the potential contributions of peripheral infection with Torque Teno virus, infection outside of and/or within the CNS with Epstein-Barr virus and infection within the CNS with Human Herpesvirus 6 to MS. An experimental animal model, Theiler's murine encephalomyelitis virus infection of susceptible strains of mice is an example of viral infections of the CNS as a prerequisite for demyelination. Finally, the proposition that multiple virus infections are required, which first prime the immune system and then trigger the disease, as a model where infections outside of the CNS lead to inflammatory changes within the CNS, for the development of a MS-like disease is explored.

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.

Purpose of Review: Potential transmission of zoonotic porcine viruses is a major safety issue in xenotransplantation. This review will first summarize recent studies involving transmission and control of the major concern, porcine endogenous retrovirus (PERV). Second, the potential for zoonotic transfer and safety measures required against other viruses of concern will be discussed., Recent Findings: As studies on PERV genomics continue, distribution of PERV, particularly porcine endogenous retrovirus-C in individual pigs in relation to their ability to transmit PERV in vitro, is becoming clearer. However, further study is required to establish pig lines devoid of problematic copies of PERV. As an extra level of safety, several strategies have been sought, with some success, to reduce PERV infectivity and be used to produce transgenic, PERV-suppressed pigs. Porcine herpesviruses, hepatitis E virus, arenaviruses and an Anellovirus, Torque teno virus, have been highlighted as other viruses of potential risk., Summary: Xenotransplantation is a unique situation in which pathogen monitoring may be required to be more comprehensive than that required for specific pathogen-free sources. With evidence of transmission of novel viruses via allotransplantation, significant attention should be paid to emerging and as yet unknown viruses.

Humans are frequently infected with three anelloviruses which have circular DNA genomes of 3.6-3.9 kb [Torque teno virus (TTV)], 2.8-2.9 kb [Torque teno mini virus (TTMV)] and 3.2 kb [a recently discovered anellovirus named Torque teno midi virus (TTMDV)]. Unexpectedly, human TTMDV DNA was not detectable in any of 74 chimpanzees tested, although all but one tested positive for both human TTV and TTMV DNA. Using universal primers for anelloviruses, novel variants of TTMDV that are phylogenetically clearly separate from human TTMDV were identified from chimpanzees, and over the entire genome, three chimpanzee TTMDV variants differed by 17.9-20.3 % from each other and by 40.4-43.6 % from all 18 reported human TTMDVs. A newly developed PCR assay that uses chimpanzee TTMDV-specific primers revealed the high prevalence of chimpanzee TTMDV in chimpanzees (63/74, 85 %) but low prevalence in humans (1/100). While variants of TTV and TTMV from chimpanzees and humans were phylogenetically interspersed, those of TTMDV were monophyletic for each species, with sequence diversity of <33 and <20 % within the 18 human and three chimpanzee TTMDV variants, respectively. Maximum within-group divergence values for TTV and TTMV were 51 and 57 %, respectively; both of these values were substantially greater than the maximum divergence among TTMDV variants (44 %), consistent with a later evolutionary emergence of TTMDV. However, substantiation of this hypothesis will require further analysis of genetic diversity using an expanded dataset of TTMDV variants in humans and chimpanzees. Similarly, the underlying mechanism of observed infrequent cross-species infection of TTMDV between humans and chimpanzees deserves further analysis.

A role for the ubiquitous Torque teno (TT) viruses in the pathogenesis of disease has not been resolved. In vivo and in vitro intragenomic rearrangement of TT virus genomes has been demonstrated. Replication in cell culture of a subviral molecule (411 bp) occurs through oligomerisation of RNA transcripts. Although the functions of the respective TT viral genes, as well as the newly formed genes in the rearranged subviral molecules, are largely unknown, certain similarities to genes of plant viruses of the family Geminiviridae will be described. A degree of similarity to certain cellular genes poses the question as to a role of molecular mimicry in the pathogenesis of autoimmune disease and diabetes.

Since 1997, groups of novel nonenveloped DNA viruses with a circular, single-stranded (negative sense) DNA genome of 3.6-3.9 kb, 3.2 kb, or 2.8-2.9 kb in size have been discovered and designated Torque teno virus (TTV), Torque teno midi virus (TTMDV), and Torque teno mini virus (TTMV), respectively, in the floating genus Anellovirus. These three anelloviruses frequently and ubiquitously infect humans, and the infections are characterized by lifelong viremia and great genetic variability. Although TTV infection has been epidemiologically suggested to be associated with many diseases including liver diseases, respiratory disorders, hematological disorders, and cancer, there is no direct causal evidence for links between TTV infection and specific clinical diseases. The pathogenetic role of TTMV and TTMDV infections remains unknown. The changing ratio of the three anelloviruses to each other over time, relative viral load, or combination of different genotype(s) of each anellovirus may be associated with the pathogenicity or the disease-inducing potential of these three human anelloviruses. To clarify their disease association, polymerase chain reaction (PCR) systems for accurately detecting, differentiating, and quantitating all of the genotypes and/or genogroups of TTV, TTMDV, and TTMV should be established and standardized, as should methods to detect past infections and immunological responses to anellovirus infections.

Objective: To determine whether porcine genogroup 1 torque teno virus (g1-TTV) can infect and cause disease in gnotobiotic swine., Sample Population: 20 conventional baby pigs and 46 gnotobiotic baby pigs., Procedures: Porcine g1-TTV was transmitted from conventional swine to gnotobiotic pigs via pooled leukocyte-rich plasmas (n=18) that had positive results for g1-TTV DNA. Bone marrow-liver homogenates that had positive results for torque teno virus (TTV) were used in 4 serial passages in gnotobiotic pigs (2 pigs/passage). A pathogenesis experiment was conducted with in vivo passages of g1-TTV in various groups of gnotobiotic pigs., Results: All g1-TTV inoculated pigs had no clinical signs but developed interstitial pneumonia, transient thymic atrophy, membranous glomerulonephropathy, and modest lymphocytic to histiocytic infiltrates in the liver after inoculation with the TTV-containing tissue homogenate; these changes were not detected in uninoculated control pigs or pigs injected with tissue homogenate devoid of TTV DNAs. In situ hybridization was used to identify g1-TTV DNAs in bone marrow mononuclear cells., Conclusions and Clinical Relevance: Analysis of these data revealed that porcine g1-TTV was readily transmitted to TTV-naïve swine and that infection was associated with characteristic pathologic changes in gnotobiotic pigs inoculated with g1-TTV. Thus, g1-TTV could be an unrecognized pathogenic viral infectious agent of swine. This indicated a directly associated induction of lesions attributable to TTV infection in swine for a virus of the genus Anellovirus.

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.

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., (Copyright 2006 John Wiley & Sons, Ltd.)

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.

The paper summarizes the updates available in the literature and the authors' own data on the etiology of hepatitis, its models, and experimental studies on susceptible simian types. A comparative analysis of the etiological agents--the causative agents of simian and human hepatitis will give a better insight into the evolution of its viruses.

Background: SEN virus (SENV) is a newly discovered DNA virus. We conducted this study to evaluate potential modes of SENV transmission and the pathogenic effect of SENV on liver diseases in children., Methods: Polymerase chain reaction was used to detect 2 SENV variant (SENV-D and SENV-H) DNA in sera from healthy individuals and diseased children. Nucleotide sequence of SENV was determined by direct sequencing., Results: SENV infection was assessed in healthy individuals, including 50 newborns (sera collected from the umbilical cord), 24 infants, 46 preschool children (aged 1-6 years), 42 school children of an age before that of the first sexual experience (aged 7-12 years), 62 adolescents (13-18 years), 72 young adults (19-30 years) and 32 adults (>30 years). The prevalence of SENV-D and/or SENV-H (SENV-D/H) viremia in each group was 0%, 17%, 24%, 24%, 27%, 33% and 40%, respectively. The prevalence of SENV-D/H viremia in 18 children with non-A to E hepatitis, 64 thalassemic children, 80 children transfused during cardiac surgery, 30 children with chronic hepatitis B, 9 children with chronic hepatitis C and 32 infants with biliary atresia was 11%, 61%, 80%, 83%, 67% and 50%, respectively. SENV was found more frequently in all patient groups than in 174 age-matched controls (P < 0.01), with the exception of non-A to E hepatitis (11% versus 24% in the control group; P = 0.27). In 2 infants with proven intrauterine hepatitis B viral infection, identical SENV-D nucleotide sequence existed in both the maternal and neonate serum. Elevated alanine aminotransferase concentrations were rarely observed in children who acquired isolated SENV viremia because of transfusion for surgery. Infection with SENV in children with chronic hepatitis C virus or hepatitis B viral infection was not associated with higher peak alanine aminotransferase values., Conclusion: SENV is transmitted mainly via nonparenteral daily contact and frequently occurs early in life. Transfusion can significantly increase the rate of SENV viremia. SENV does not appear to cause hepatitis in children.

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.

A sequence-independent PCR amplification method was used to identify viral nucleic acids in the plasma samples of 25 individuals presenting with symptoms of acute viral infection following high-risk behavior for human immunodeficiency virus type 1 transmission. GB virus C/hepatitis G virus was identified in three individuals and hepatitis B virus in one individual. Three previously undescribed DNA viruses were also detected, a parvovirus and two viruses related to TT virus (TTV). Nucleic acids in human plasma that were distantly related to bacterial sequences or with no detectable similarities to known sequences were also found. Nearly complete viral genome sequencing and phylogenetic analysis confirmed the presence of a new parvovirus distinct from known human and animal parvoviruses and of two related TTV-like viruses highly divergent from both the TTV and TTV-like minivirus groups. The detection of two previously undescribed viral species in a small group of individuals presenting acute viral syndrome with unknown etiology indicates that a rich yield of new human viruses may be readily identifiable using simple methods of sequence-independent nucleic acid amplification and limited sequencing.

TT virus (TTV) is widespread among the global population. Its pathogenic nature is still unclear but TTV seems to be more prevalent in cases of hepatitis than in healthy individuals. TTV harbours similarities to chicken anaemia virus (CAV). Here, the apoptotic potential of a putative TTV-derived 105 aa protein and of the main apoptosis-inducing agent of CAV, Apoptin, is compared. As the putative protein induced apoptosis in various human hepatocellular carcinoma (HCC) cell lines, it was named TTV-derived apoptosis-inducing protein (TAIP). The apoptotic activity of TAIP in HCC lines was comparable with that of Apoptin. Conversely, unlike Apoptin, TAIP induced only low-level apoptosis in several non-HCC human cancer cell lines. The data suggest that TAIP acts in a different way to Apoptin as it is selective to a certain degree for HCC lines. This activity of TAIP, coupled with the heterogeneity of TTV isolates, may help to explain the variable reports of TTV pathogenicity.

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., (Copyright 2003 Wiley-Liss, Inc.)

The paper reviews the available information on the newly discovered viruses originally supposed to cause post-transfusion hepatitis. GBV-C/Hepatitis G virus belongs to the Flaviviridae family, and can be transmitted parenterally like Hepatitis C virus. Its role in causing hepatitis or other diseases has not been proved yet. The other newly discovered viruses contain single-stranded circular DNA, with a wide range of sequence divergence. These viruses can be transmitted not only with blood and blood products but via fecal-oral route as well. They are unique among enterally transmitted viruses in the sense that the virus persists for years in the human body, therefore their genomes may be detected in the blood of the healthy population in high percentage. One of the genotypes of TTV is suspected to cause hepatitis. High TT virus load was found as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease. It is not clear yet, whether TTV-like minivirus and SEN virus cause any illnesses.

Serum samples from healthy and diseased children were studied for the presence of TTV DNA by nested PCR using primer sets generated from N-22 region and from the untranslated region (UTR) of the viral genome. N-22 positive TTV DNA was detectable in 33 (27%) of 122 healthy children, 47 (73.4%) of 64 polytransfused thalassemic children, 37 (46.3%) of 80 children who received transfusion during cardiac surgery, 8 (42.1%) of 19 non-A to E hepatitis, 10 (33.3%) of 30 HBV carrier children, and 5 (15.6%) of 32 infants with biliary atresia. A much higher prevalence of TTV DNA with rates varying from 78-100% in the above study groups was observed using the UTR primers. For children with N-22 positive TTV DNA, biochemical assessment of isolated TTV viremia in thalassemic children or children transfused during surgery showed no convincing association between raised ALT levels and TTV viremia. Coinfection with TTV in chronic HCV-infected or HBV-infected children did not result in higher peak ALT levels during follow-up, suggesting that TTV has no synergistic pathogenic effect. The phylogenetic analysis of the N-22 positive TTV DNA isolates revealed that most isolates from healthy children, children transfused during surgery, and non-A to E fulminant hepatitis children were type 1 TTV. These results indicate that TTV infection in children was significantly associated with transfusion. TTV infection is highly prevalent in early childhood in Taiwan but plays a minimal role in the induction of hepatitis in children., (Copyright 2003 Wiley-Liss, Inc.)

Hepatitis B and C viruses (HBV and HCV) have been associated with hepatocellular carcinoma (HCC). Recently, a novel DNA virus was isolated from a patient with posttransfusion hepatitis of unknown etiology and designated TT virus (TTV). To examine whether this virus is associated with HCC, we investigated sera from 82 Egyptian patients with histopathologically-diagnosed HCC. All subjects underwent serological investigations for detection of hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HbcAb) and anti-HCV. Detection of TTV-DNA was performed by semi-nested polymerase chain reaction (PCR) using TTV-specific primers. TTV-DNA was detected in 28% of the patients. Age, gender, risk factors and biochemical liver functions did not significantly differ between TTV-DNA positive and negative patients. TTV was detected in 27.1% of patients with HCV-HCC, 25% of HBV-HCC, 66.7% of dual HCV and HBV infection and 40% of those with non-B, non-C-HCC (NBNC-HCC). It is concluded that, in this the cohort of Egyptian patients with HCC, TTV infection is common and is not associated with HCV, HBV, NBNC-HCC, history of schistosomiasis or blood transfusion.

Background/aims: TT virus is a novel DNA virus that is associated with posttransfusion hepatitis. The prevalence, risk factors, and clinical significance of TT virus infection were evaluated in patients with chronic renal failure who are on hemodialysis., Methodology: Nested polymerase chain reaction was used to test for TT virus DNA in the serum of patients on hemodialysis as well as in healthy controls., Results: TT virus DNA was detected in 15 (20.0%) of the 75 patients on hemodialysis and 10 (13.2%) of the 76 healthy controls (P > 0.05). In chronic renal failure patients on hemodialysis, the prevalence of TT virus did not differ according to the duration of hemodialysis or the amount of blood transfusion. The prevalence of TT virus was higher in IgG anti-hepatitis B core antibody-positive patients than IgG anti-hepatitis B core antibody-negative patients (27.5% vs. 4.2%, P = 0.03). Two (13.3%) of the 15 TT virus-positive and 6 (10.0%) of the 60 TT virus-negative patients showed elevated alanine aminotransferase levels (P > 0.05)., Conclusions: TT virus infection did not occur more frequently in patients on hemodialysis than in healthy controls. No relationship was found between TT virus infection and liver disease. The correlation between TT virus infection and IgG anti-hepatitis B core antibody suggests that TT virus may share some routes of transmission with hepatitis B virus.