Elevated levels of Merkel cell polyoma virus in the anophthalmic conjunctiva.

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.

Torque Teno Virus Load Is Associated With Subclinical Alloreactivity in Kidney Transplant Recipients: A Prospective Observational Trial.

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 (ß 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.

Prevalence, incidence and residual risk of transfusion transmitted viruses (HBV, HCV and HIV infections) in Lithuanian blood donors from 2004 to 2018: The incidence/window-period model study.

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.

Torque teno virus in liver diseases: On the way towards unity of view.

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.

Detection of Torque Teno Virus (TTV) and TTV-Like Minivirus in patients with presumed infectious endophthalmitis in India.

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.

Torque teno virus viral load is related to age, CMV infection and HLA type but not to Alzheimer's disease.

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.

Molecular prevalence and genotypes of human pegivirus-1 (HPgV-1) and SENV-like viruses among multiply transfused patients with beta-thalassemia.

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.

Genetic Analysis and Evolutionary Changes of the Torque teno sus Virus.

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.

Torque Teno Virus for Risk Stratification of Acute Biopsy-Proven Alloreactivity in Kidney Transplant Recipients.

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.

Infectious agents and different course of multiple sclerosis: a systematic review.

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.

The kinetics of torque teno virus plasma DNA load shortly after engraftment predicts the risk of high-level CMV DNAemia in allogeneic hematopoietic stem cell transplant recipients.

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 log10 TTV DNA loads quantified by days 20 and 30 after transplantation (TTV DNA load AUC20-30), 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 AUC20-30⩽2.8 copies × days × mL-1 were more likely to have high-level CMV DNAemia. A trend towards a direct correlation between TTV DNA AUC20-30 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.

Transplacental transmission of torque teno virus.

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 × 104 copies/mL; range: 103 - 3 × 107). 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.

Torque Teno Virus Load-Inverse Association With Antibody-Mediated Rejection After Kidney Transplantation.

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.

Lack of strong anti-viral immune gene stimulation in Torque Teno Sus Virus1 infected macrophage cells.

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-ß 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.

The pathogenic role of torque teno sus virus 1 and 2 and their correlations with various viral pathogens and host immunocytes in wasting pigs.

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.

Does Teno Torque Virus Induce Autoimmunity After Hematopoietic Stem Cell Transplantation? A Case Report.

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.

Torque teno sus virus (TTSuV) infection at different stages of pig production cycle / Infecção pelo Torque teno sus virus (TTSuV) em diferentes categorias do ciclo de produção de suínos

Torque teno sus virus (TTSuV) infection is present in pig herds worldwide. It has been demonstrated that TTSuV might increase the severity of other important viral diseases with economic and public health impacts. At present, there is no information on the age distribution of pigs infected with TTSuV in Brazilian herds. This study evaluated the frequency of TTSuV infection in pigs at different stages of production. Fecal samples (n=190) from pigs at 1 to 24 weeks of age and from breeders at 6 farrow-to-weaning (up to 8 weeks of age) and 9 grower-to-finish (9 weeks of age onwards) farms in the western region of Paraná state, Brazil, were evaluated by PCR. Fragments of the 5' UTRs of TTSuV1 and/or TTSuVk2 DNAs were identified in 126 (66.3%) of the fecal samples. Significant differences were found with the percentages of positive samples for TTSuV1, TTSuVk2, and mixed infections by both genera between and within the different pig production stages. Fecal samples from the grower-to-finish farms had TTSuV detection rates (90.1%; 64/71) that were significantly (p<0.05) higher than those from the farrow-to-weaning farms (52.1%; 62/119). TTSuV detection was significantly (p<0.05) more frequent in finisher pigs than in the animals from the other stages. The UTR nucleotide sequences in this study presented higher similarities to strains from Norway (96%, TTSuV1), and Argentina and China (97.1%, TTSuVk2). These results suggest that TTSuV infection has spread to pigs of all production stages and that the viral infection rate increases with the age of the animals. In the western region of Paraná state, Brazil, TTSuV1 and TTSuVk2-induced infections were more frequently observed in suckling piglets and finisher pigs, respectively. Phylogenetic analysis pointed out the possibility of different strains of TTSuV1 and TTSuVk2 circulating in pig herds of Brazil.

A infecção pelo Torque teno sus virus (TTSuV) está presente em rebanhos suinícolas em todo o mundo. Tem sido demonstrado que a infecção pelo TTSuV pode aumentar a gravidade de outras importantes doenças virais com impactos econômicos e na saúde pública. Atualmente não há informações sobre a distribuição da infecção pelo TTSuV, de acordo com a faixa etária, em rebanhos suinícolas brasileiros. Este estudo avaliou a frequência da infecção pelo TTSuV nas diferentes categorias de produção de suínos. Amostras fecais (n=190) de suínos com 1 a 24 semanas de idade e de reprodutores provenientes 6 unidades produtoras de leitão (até 8 semanas de idade) e 9 unidades de terminação (9 semanas de idade em diante) da região oeste do Paraná, Brasil, foram avaliadas pela técnica de PCR. Fragmentos da região 5' UTR do DNA do TTSuV1 e/ou TTSuVk2 foram identificados em 126 (66,3%) amostras fecais. Diferenças significativas foram encontradas em relação às porcentagens de amostras positivas para o TTSuV1, TTSuVk2 e infecção mista por ambos os gêneros inter e intra categorias. Amostras fecais provenientes de unidades de terminação apresentaram taxas de detecção de TTSuV (90.1%; 64/71) significativamente (p<0.05) mais altas do que aquelas provenientes de unidades produtoras de leitão (52.1%; 62/119). A detecção do TTSuV em animais de terminação foi significativamente (p<0.05) mais frequente do que nos suínos de outras categorias. As sequências de nucleotídeos da UTR deste estudo apresentaram maior similaridade com cepas da Noruega (96%, TTSuV1) e Argentina e China (97,1%, TTSuVk2). Estes resultados sugerem que a infecção pelo TTSuV encontra-se disseminada em suínos de todas as categorias de produção e que a taxa da infecção viral aumenta de acordo com a idade dos animais. Na região oeste do estado do Paraná, infecções induzidas pelo TTSuV1 e TTSuVk2 foram mais frequentemente observadas em leitões de maternidade e suínos de terminação, respectivamente. A análise filogenética indicou a possibilidade de diferentes cepas de TTSuV1 e TTSuVk2 circulando em rebanhos suinícolas brasileiros.

Prevalence and assessment of role of SEN virus in acute and chronic hepatitis in India.

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.

Discovery of a novel Torque teno sus virus species: genetic characterization, epidemiological assessment and disease association.

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.