Search Results (47)

Currently, approximately 90,000 patients are on the kidney transplant waitlist in the United States, including 10,000 individuals awaiting re-transplantation due to prior graft failure. Allograft rejection remains a leading cause of kidney transplant failure. While the current gold standard for diagnosing rejection is tissue biopsy, it is invasive and impractical for routine or longitudinal graft surveillance. This review summarizes the current landscape of non-invasive biomarkers for detecting and predicting kidney transplant rejection, with a focus on both historical context and recent advancements. In particular, we highlight the roles of donor-derived cell-free DNA (dd-cfDNA) and gene expression profiling (GEP) in identifying acute rejection. We also discuss emerging biomarkers such as torque teno virus (TTV), which has shown potential as an indirect indicator of immunosuppression levels and rejection risk. Importantly, this review excludes biomarker studies that rely on tissue biopsy, emphasizing non-invasive approaches to rejection monitoring. Full article

Xenobiotics are non-natural chemical compounds to which the human population is exposed. Chronic exposure to certain xenobiotics is associated with various diseases, including cancer development. Anelloviruses (AVs), including Torque Teno Virus (TTV), Torque Teno Mini Virus (TTMV), and Torque Teno Midi Virus (TTMDV), are ubiquitous viruses found in the general population. As no disease has been definitively associated with AVs, they are sometimes referred to as “viruses awaiting a disease”. This review explores the potential roles of xenobiotics and AVs in colorectal cancer (CRC) development and suggests a potential interplay between them. Evidence suggests an association between certain xenobiotics (like pesticides, cigarette smoke components, and dietary factors) and CRC, while such an association is less clear for AVs. The high prevalence of AVs suggests these infections alone may be insufficient to disrupt homeostasis; thus, additional factors might be required to promote disease, potentially including cancer. Full article

Background/Objectives: New monitoring methods are being developed to improve the kidney transplant outcome. Among them, the measurement of Torque Teno virus load (TTV load) has been associated with the overall immunosuppressive status and the percentage of donor-derived circulating free DNA (dd-cfDNA) with molecular graft injury, mainly related to antibody-mediated rejection (AbMR). Both methods provide complementary information, but they have not been previously used together for the monitoring of kidney transplant recipients (KTx). Methods: A prospective study including 42 KTx performed in our centre was conducted, in which we monitored dd-cfDNA using a targeted NGS assay (AlloSeq cfDNA) in the first month and the TTV load with in-house PCR in the first and third months. Results: Eleven KTx with high molecular injury defined by dd-cfDNA ≥ 1.0% were selected. The TTV load showed a non-significant trend of being lower in AbMR patients (2.91, IQR 4.18 vs. 3.48, IQR 1.47 log10 copies/mL, p = 0.788). No overimmunosuppressed patient developed AbMR, whereas 40% of non-overimmunosuppressed patients showed AbMR (p = 0.428). The TTV load increased more in the AbMR-treated KTx (0.00, IQR 4.71 vs. +6.58, IQR 4.04 log10 copies/mL, p = 0.042) from months one to three, with all AbMR-treated KTx becoming overimmunosuppressed. KTx with opportunistic infections showed higher TTV loads in the third month (5.18, IQR 5.92 vs. 11.53, IQR 3.54 log10 copies/mL, p = 0.024). Conclusions: KTx with molecular injury secondary to rejection tended to be less immunosuppressed, as indicated by a low TTV load. After AbMR therapy, all KTx became overimmunosuppressed and suffered a higher risk of opportunistic infections. Dual monitoring provides useful complementary information for the follow-up of kidney transplant recipients. Full article

After transplantation, systematically monitoring and assessing the risk of transplanted organ rejection is crucial. Current methods involving immunosuppressant monitoring, the assessment of organ function, and biopsies are insufficient for predicting rejection. However, regular determination of torque teno virus (TTV) load after transplantation may prove to be a useful parameter for monitoring immunosuppression efficacy. Therefore, we aimed to evaluate TTV load in patients before and after lung transplantation and the kinetics of TTV growth in relation to immunosuppression strength. We included 14 patients (mean age: 49.4 ± 14.0 years) undergoing lung transplantation and determined TTV copy numbers using the commercial ARGENE TTV-R-GENE kit from BioMerieux from the day of transplantation to 180 days post-transplantation. We also developed an empirical immunosuppression unit scale to calculate immunosuppression strength. We observed an average positive correlation between log₁₀ TTV and immunosuppression strength, with significant increases in log₁₀ TTV depending on the duration of immunosuppression. These results indicate the potential of TTV as a new parameter to assess the possibility of transplanted organ rejection. Full article

Pigs serve as critical reservoirs and amplifiers for numerous zoonotic viral diseases, presenting substantial public health challenges in India. This study highlights the epidemiology and emerging trends of key zoonotic viruses associated with pigs, emphasizing their role in endemic and emerging disease dynamics. Japanese encephalitis virus (JEV) persists as a major concern, with pigs acting as amplifying host, while hepatitis E virus (HEV) remains a prominent cause of viral hepatitis, transmitted via contaminated water and pork products. Emerging high-fatality viral zoonoses caused by Nipah virus (NiV) and recurrent threats from swine influenza virus (SIV) demonstrate that the zoonotic landscape is evolving. Furthermore, zoonotic viruses like rotavirus, pseudorabies (ADV or SuHV-1), porcine astrovirus (PAstV), and Torque teno sus virus (TTSuV) reflect the expanding diversity of pig-associated pathogens in India. Emerging evidence also implicates viruses such as Chandipura virus (CHPV) in localized outbreaks, indicating broader zoonotic potential. Novel risks such as swine acute diarrhea syndrome coronavirus (SADS-CoV) and SARS-CoV-2 emphasize the role of pigs as potential intermediaries for pandemic-prone viruses. This comprehensive study evaluates the prevalence, outbreak dynamics, and public health implications of zoonotic viral diseases of pigs in India, providing valuable direction for developing effective control measures. Full article

Torque Teno Virus (TTV) is a highly prevalent non-pathogenic DNA virus whose plasma levels may be related to the host’s immune status. TTV gained attention about 25 years ago, but its replication is not fully understood, nor is its relationship with the host's immune system. Despite this lack of knowledge, TTV is currently being investigated as a functional biomarker of the immune system in patients with immunological damage and inflammatory diseases. Monitoring TTV viral load over time may help clinicians in making therapeutic decisions regarding immunosuppression as well as the likelihood of infectious complications. This review summarizes what we do and do not know about this enigmatic virus. Full article

Monitoring immune function in post-transplant patients is crucial to reduce the risk of viral infections (e.g., cytomegalovirus [CMV] or Epstein–Barr virus [EBV]), which can lead to serious complications such as post-transplant lymphoproliferative disorder (PTLD). Recently, Torque Teno virus (TTV) has attracted interest as a marker of immune function. Thus, we studied the kinetics of common post-transplant viral infections (TTV, EBV, CMV, human herpesvirus-6 [HHV-6], and adenovirus [AdV]) and their association with clinical parameters in 23 HSCT recipients who developed PTLD (PTLD-HSCT) and 25 post-HSCT patients without PTLD (Non-PTLD-HSCT) at three different timepoints: at the time of the transplant (T0), 3 months (T1), and 6 months (T2) post-HSCT. Additionally, 25 healthy donors (HD) were used as the control. EBV, CMV, HHV-6, or AdV infections were found in a few samples, while TTV was found in all of our samples. The highest TTV levels (4.61 [T0], 6.24 [T1] and 6.70 [T2] log₁₀ copies/mL) were seen in PTLD-HSCT patients compared to Non-PTLD-HSCT (3.39 [T0], 4.86 [T1], and 3.75 [T2] log₁₀ copies/mL) and HD (2.25 log₁₀ copies/mL) at all timepoints. Higher TTV levels were also seen in patients with a destructive type of PTLD and in surviving PTLD-HSCT patients compared to deceased ones. TTV kinetics in PTLD patients post-HSCT showed that TTV levels increase with the fall in the host immunocompetence and that by monitoring TTV kinetics, the immune status of the patient can be monitored. Full article

Viral infections are one of the most important causes of morbidity and mortality among patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Immunosuppression may lead to the reactivation of latent viruses or the acquisition of new infections, resulting in severe clinical outcomes. The early detection of viral reactivations is crucial for effective patient management and post-transplant care. In this study, we employed next-generation metagenomics to assess changes in viral abundance and detect clinically significant viruses in allogeneic HSCT patients. A total of 20 patients from the Transplant Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo were included, with plasma samples collected at three time points: D + 0 (pre-transplantation), D + 30 (30 days post-transplantation), and D + 100 (~100 days post-transplantation). A higher presence of clinically relevant viruses, such as the cytomegalovirus (CMV), the Epstein-Barr virus (EBV) and adenoviruses, were predominantly detected at D + 30. The diversity of commensal viruses, primarily anelloviruses, increased gradually, with the highest abundance and variability detected at D + 100. Viruses with clinical importance for HSCT, including CMV, adenovirus and EBV, were confirmed and characterized at the molecular level, showing generally high cycle threshold values. Our findings demonstrate a rise in anellovirus abundance following allogeneic HSCT, with the highest levels observed at D + 100. Notably, D + 30 was identified as a critical time point for the reactivation of clinically significant viruses. This study underscores the potential of metagenomics in the identification of clinically relevant viruses and highlights the importance of monitoring latent viruses in immunocompromised populations, including allogeneic HSCT patients. Full article

Torque teno virus (TTV) is a ssDNA orphan virus belonging to the Anelloviridae family, but some recent studies suggested its possible involvement in central nervous system (CNS) pathology. We analyzed serum and cerebrospinal fluid samples (CSF) from 109 patients with encephalitis for TTV infection using serological and molecular testing, virus quantitative measurement, and next-generation sequencing-based (NGS) phylogenetic analysis. TTV noncoding region (UTR) and/or open reading frame 1 (ORF-1) sequences were detected in serum of 86 (79%) patients and in nine (8%) patients in CSF. Five of the latter patients were coinfected with various entero- and herpesviruses. Anti-TTV-IgG were detected in 80 (73.4%) sera and in two (1.8%) CSF samples, while anti-TTV-IgM were present in three (2.8%) sera and in none of the CSFs. Phylogenic analysis of CSF-derived TTV ORF-1 sequences revealed the presence of three unique variants in one patient. TTV was quantified in five CSF-serum pairs: in two patients viral loads were similar, and in three serum TTV loads were approximately one log higher. Our results suggest at least an occasional replication of TTV in CNS. However, whether TTV could be the cause of encephalitis requires further studies. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder classified by the WHO as postviral fatigue syndrome (ICD-11 8E49 code). Diagnosing ME/CFS, often overlapping with fibromyalgia (FM), is challenging due to nonspecific symptoms and lack of biomarkers. The etiology of ME/CFS and FM is poorly understood, but evidence suggests viral infections play a critical role. This study employs microarray technology to quantitate viral RNA levels in immune cells from ME/CFS, FM, or co-diagnosed cases, and healthy controls. The results show significant overexpression of the Torque Teno Mini Virus 9 (TTMV9) in a subgroup of ME/CFS patients which correlate with abnormal HERV and immunological profiles. Increased levels of TTMV9 transcripts accurately discriminate this subgroup of ME/CFS patients from the other study groups, showcasing its potential as biomarker for patient stratification and the need for further research into its role in the disease. Validation of the findings seems granted in extended cohorts by continuation studies. Full article

Understanding the epidemiology and transmission dynamics of transboundary animal diseases (TADs) among wild pigs (Sus scrofa) will aid in preventing the introduction or containment of TADs among wild populations. Given the challenges associated with studying TADs in free-ranging populations, a surrogate pathogen system may predict how pathogens may circulate and be maintained within wild free-ranging swine populations, how they may spill over into domestic populations, and how management actions may impact transmission. We assessed the suitability of Torque teno sus virus 1 (TTSuV1) to serve as a surrogate pathogen for molecular epidemiological studies in wild pigs by investigating the prevalence, persistence, correlation with host health status and genetic variability at two study areas: Archbold’s Buck Island Ranch in Florida and Savannah River Site in South Carolina. We then conducted a molecular epidemiological case study within Archbold’s Buck Island Ranch site to determine how analysis of this pathogen could inform transmission dynamics of a directly transmitted virus. Prevalence was high in both study areas (40%, n = 190), and phylogenetic analyses revealed high levels of genetic variability within and between study areas. Our case study showed that pairwise host relatedness and geographic distance were highly correlated to pairwise viral genetic similarity. Molecular epidemiological analyses revealed a distinct pattern of direct transmission from pig to pig occurring within and between family groups. Our results suggest that TTSuV1 is highly suitable for molecular epidemiological analyses and will be useful for future studies of transmission dynamics in wild free-ranging pigs. Full article

Anelloviruses are ubiquitous in humans and represent a major component of the human virome. Its best-known representative is Torque teno virus (i.e., the Alphatorquevirus genus), which is considered a potential immunity biomarker. Recent metagenomic investigations revealed not only the extraordinary genomic diversity of anellovirus sequences, but also that co-detection of genera, genotypes, or species seems to be the rule in humans. SCANellome was developed to represent a user-friendly tool to analyze the primate (both human and non-human) anellovirus composition at the genus, species, and genotype level from metagenomics data based on an up-to-date database. This SCANellome update includes >900 additional reference sequences from GenBank. Using a clustering at 90% identity, the FASTA database was updated and generated 134 new representative sequences. Based on ORF1, the analysis of these new sequences indicates the presence of 206 potential new species, including four nonhuman primates, and adds four new non-human primate species which will be the subject of a proposal to the International Committee on Taxonomy of Viruses (ICTV). In addition, SCANellome V2 provides now the user with an interactive up-to-date phylogenetic analysis (of ORF1) to show the distribution among the 12 human and nonhuman primate genera of these new potential species. Finally, the Anelloviridae taxonomy was updated to rename species names in binomial format as required by the ICTV. Full article

Torque Teno Virus (TTV) is a ubiquitous component of the human virome, not associated with any disease. As its load increases when the immune system is compromised, such as in kidney transplant (KT) recipients, TTV load monitoring has been proposed as a method to assess immunosuppression. In this prospective study, TTV load was measured in plasma and urine samples from 42 KT recipients, immediately before KT and in the first 150 days after it. Data obtained suggest that TTV could be a relevant marker for evaluating immune status and could be used as a guide to predict the onset of infectious complications in the follow-up of KT recipients. Since we observed no differences considering distance from transplantation, while we found a changing trend in days before viral infections, we suggest to consider changes over time in the same subjects, irrespective of time distance from transplantation. Full article

Pneumoconiosis is a common occupational disease that can worsen with accompanying infection. Torque teno virus (TTV) is a prevalent human virus with multiple genotypes that can chronically and persistently infect individuals. However, the prevalence of TTV in pneumoconiosis patients is still unclear. This research aims to detect the presence and prevalence of TTV in the alveolar lavage fluid of pneumoconiosis patients in the Hunan Province of China using PCR. As a result, a 65.5% positive rate (19 out of 29) of TTV was detected. The TTV detection rate varies among different stages of silicosis and different pneumoconiosis patient ages. Nine novel TTV genomes ranging in size from 3719 to 3908 nt, named TTV HNPP1, HNPP2, HNPP3, HNPP4, HNPP5, HNPP6-1, HNPP6-2, HNPP7-1 and HNPP7-2, were identified. A genomic comparison and phylogenetic analysis indicated that these nine TTVs represent five different species with high genetic diversity which belong to the genus Alphatorquevirus. HNPP6-1 and HNPP6-2 belong to TTV3, HNPP5 belongs to TTV13, HNPP1 belongs to TTV24, HNPP4 belongs to TTV20, and the others belong to TTV19. The genomes of TTV HNPP1, HNPP6-1, and HNPP6-2 contain three putative open reading frames (ORFs) coding for proteins, ORF1, ORF2, and ORF3, while the other six TTV genomes contain two ORFs coding for proteins, ORF1 and ORF2. These results provide the first description of TTV epidemiology in pneumoconiosis patients in China. The newly identified TTV genome sequences reveal the high genetic diversity of TTV in pneumoconiosis patients and could contribute to a deeper understanding of TTV retention and infection in humans. Full article

Tibetan pig is a unique pig breed native to the Qinghai–Tibet Plateau. To investigate viral communities associated with porcine respiratory disease complex (PRDC), 167 respiratory samples were collected from Tibetan pigs in the Ganzi Tibetan autonomous prefecture of Sichuan province. Following library construction and Illunima Novaseq sequencing, 18 distinct viruses belonging to 15 viral taxonomic families were identified in Tibetan pigs with PRDC. Among the 18 detected viruses, 3 viruses were associated with PRDC, including porcine circovirus type 2 (PCV-2), Torque teno sus virus (TTSuV), and porcine cytomegalovirus (PCMV). The genomic sequences of two PCV-2 strains, three TTSuV strains, and one novel Porprismacovirus strain were assembled by SOAPdenovo software (v2). Sequence alignment and phylogenetic analysis showed that both PCV-2 strains belonged to PCV-2d, three TTSuVs were classified to TTSuV2a and TTSuV2b genotypes, and the Porprismacovirus strain PPMV-SCgz-2022 showed a close genetic relationship with a virus of human origin. Recombination analysis indicated that PPMV-SCgz-2022 may have originated from recombination events between Human 16,806 × 66-213 strain and Porcine 17,668 × 82-593 strain. Furthermore, the high proportion of single infection or co-infection of PCV2/TTSuV2 provides insight into PRDC infection in Tibetan pigs. This is the first report of the viral communities in PRDC-affected Tibetan pigs in this region, and the results provides reference for the prevention and control of respiratory diseases in these animals. Full article