Torque Teno Research Articles

Strong association of Torque teno virus/Torque teno-like minivirus to Kikuchi-Fujimoto lymphadenitis (histiocytic necrotizing lymphadenitis) on quantitative analysis.

Kikuchi-Fujimoto disease (KFD) is a rare benign lymphadenitis that mainly involves cervical lymph nodes of young Asian women with unknown etiology. Recently, we experienced a case of KFD found with Torque teno virus/Torque teno-like mini virus (TTV/TTMV) from a 26-year-old woman. TTV/TTMV is a genus of Circoviridae that causes necrotizing lymphadenitis in pigs, which shares the key histologic finding of KFD. The purpose of this study is to investigate the pathogenic role of TTV/TTMV in KFD by quantitative polymerase chain reaction (qPCR) analysis. We performed two-step qPCR specific to TTV/TTMV with formalin-fixed paraffin-embedded tissue of sequentially selected 100 KFD patients and 50 randomly selected, matched normal controls. Consequent direct sequencing was done for confirmation with PCR products. PCR amplification of TTV and TTMV was found in a significantly higher proportion in KFDs than normal controls (TTV, 85% vs. 18%, p < 0.000; TTMV, 91% vs. 24%, p < 0.000). After the sequencing, KFD samples showed more sequence matching than control samples for TTMV (94% vs. 30%, p < 0.000). This finding strongly suggests the possible implication of TTV/TTMV in the pathogenesis of KFD. Animal or in vivo experimental design should be followed in the future.Key Points• Kikuchi-Fujimoto disease (KFD) is rare and its etiology is still unclear.• Torque teno/Torque teno-like minivirus (TTV/TTMV) is a recently introduced virus in the Circoviridae family that causes necrotizing lymphadenitis in pigs, histologically similar to KFD.• We discovered the significantly increased TTV/TTMV viral loads in the KFD patients than normal controls, which implicates TTV/TTMV in the pathogenesis of KFD.

The Role of Emerging and Neglected Viruses in the Etiology of Hepatitis.

In this review, we present the overview of emerging and neglected viruses associated with liver involvement. Hepatitis E virus (HEV) emerged in the last two decades, causing hepatitis in many parts of the world. Moreover, liver involvement was also described in some emerging arboviral infections. Many reports showed dengue-associated liver injury; however, chikungunya, West Nile, tick-borne encephalitis, and Zika virus are rarely associated with clinically manifest liver disease. In addition, some neglected highly prevalent viruses such as adenoviruses and parvovirus B19 are capable of causing hepatitis in specific population groups. Anelloviruses (torque teno virus/torque teno mini virus/torque teno midi virus, SEN virus), human bocavirus, pegiviruses, and lymphocytic choriomeningitis virus have shown a little potential for causing hepatitis, but their role in the etiology of liver disease remains to be determined. In addition to the well-known hepatotropic viruses, many emerging and neglected viruses have been associated with liver diseases. The number of emerging zoonotic viruses has been increasingly recognized. While zoonotic potential of HEV is well documented, the recent identification of new hepatitis-related animal viruses such as HEV strains from rabbits and camels, non-primate hepaciviruses in domestic dogs and horses, as well as equine and porcine pegivirus highlights the possible zoonotic transmission in the context of "One Health." However, zoonotic potential and hepatotropism of animal hepatitis viruses remain to be determined.

The Value of Torque Teno Virus (TTV) as a Marker for the Degree of Immunosuppression in Adult Patients after Hematopoietic Stem Cell Transplantation (HSCT)

Torque teno virus (TTV) is a nonenveloped, single-stranded, circular DNA virus of the family of Anelloviridae. The first contact with TTV usually occurs in early childhood, followed by persistent infection in bone marrow and lymphocytes. Increased levels of TTV-DNA are found in the serum in various states of immune deficiency. The objective of this study was to assess if monitoring of TTV viremia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a predictive marker for immune-related clinical complications. In a retrospective study, 2054 whole-blood samples from 123 patients were tested for viral loads of TTV-DNA by real-time PCR within 345 days after allo-HSCT. We enrolled all patients who underwent allo-HSCT between September 2015 and April 2018. Clinical and laboratory data were collected and statistically analyzed. Patients with an underlying lymphatic malignancy had significantly higher torque teno (TT) viral loads compared with patients with an underlying malignant myeloid disease (P < .05). Complete remission before allo-HSCT correlated significantly with higher TT viral loads after allo-HSCT (P < .05). Myeloablative conditioning regimens led to significantly higher TT viral loads than reduced-intensity conditioning regimens (P < .05). A higher anti-thymocyte globulin (ATG) dose was associated with a significantly higher TT viral load. We did not observe any significant differences of TT viral load correlating with accompanying clinically relevant events such as virus reactivations (cytomegalovirus, Epstein-Barr virus, Adenovirus), acute graft-versus-host disease (aGVHD), relapse, or death. TT viral load after allo-HSCT did weakly correlate with T cell, T suppressor cell, T helper cell, and natural killer and B cell count. Although statistically significant differences between study groups were observed, virus reactivations, aGVHD, and clinical outcomes could not be predicted by monitoring TTV viremia. Therefore, TTV seems not to be suitable as a marker for the degree of immunosuppression or as a prognostic marker for clinically critical events in patients after allo-HSCT.

Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Hepatitis B virus (HBV) reactivation in immunosuppressed patients can cause considerable morbidity and mortality. The aim of our study was to evaluate factors associated with acute liver failure (ALF) in HBV reactivation. Clinical, laboratory, and virological data of 87 patients with HBV reactivation were analyzed retrospectively. Teno torque virus (TTV) plasma loads were measured as a measure of immune competence. HBV genomes isolated from 47 patients were analyzed by next-generation sequencing. A functional analysis of identified HBsAg mutants was performed. In patients with ALF the diagnosis was significantly later confirmed than in the non-ALF group. Patients diagnosed during immunosuppression had a milder clinical course compared to later diagnosed patients (p = 0.018, OR = 4.17). TTV viral loads did not differ significantly between the two groups. The HBV genomes isolated from ALF patients had higher viral complexity. A mutation in C-region of HBsAg (L216*), was associated with reduced HBsAg production and secretion. Patients diagnosed with HBV reactivation during immunosuppression had a milder clinical course compared to patients diagnosed during immune reconstitution. ALF was associated with higher viral complexity. An HBsAg mutation (L216*) was found to be more frequent in ALF patients and was associated with reduced HBsAg production and secretion.

Study the prevalence of torque teno (TT) virus infection in patients with hematological malignancies

Torque Teno (TT) virus infection may increase the risk of different types of leukemia. In this study the infective markers of TT virus, hepatitis B virus (HBV), and hepatitis C virus (HCV) were evaluated in patients with different types of leukemia in comparison with controls. In this cross sectional study Ethylenediaminetetraacetic acid (EDTA)-treated blood samples were collected from 163 patients with leukemia and 100 control between years: 2007-2011. Molecular prevalence of TT virus infection was evaluated in studied populations using in-house semi-nested polymerase chain reaction (PCR) protocol. HBsAg and HCVAb were analyzed in studied groups by third generation ELISA kits according to manufacturer’s instructions. The genomic DNA of TT virus was found in 29 of 163 (17.8%) of leukemia patients and 2 of 100 (2%) of controls. HBsAg was diagnosed in 21 of 147 (14.3%) patients with leukemia and in 2 of 100 (2%) controls. HCVAb was diagnosed in 4 of 147 (2.7%) patients with leukemia and in none of controls. The co-infection of TT virus with HBV and with HCV was found in 4 of 147 (2.7%) and in 1 of 147 (0.7%) of patients with leukemia, respectively. Identification of high prevalence of TT virus infection in patients with leukemia compared with controls emphasize on possible association between TT virus infections with leukemia. Therefore evaluation of the prevalence of TT viral infection in larger groups of patients with long lasting follow up is suggested. Key words: Torque Teno (TT) virus, hepatitis B virus (HBV), hepatitis C virus (HCV), leukemia, hematological malignancies.

High Prevalence of Torque Teno (TT) Virus in Classical Kaposi's Sarcoma

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