The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy

Abstract

IntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer.MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review.ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001).ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.

Quantification of Torque Teno Virus (TTV) in plasma and saliva of individuals with liver cirrhosis: a cross sectional study

“…In saliva, despite the extremely high mean of TTV viral load (49,542.83 copies/mL), one can observe a high standard deviation in which the great majority of the patients (percentile 75) also had much lower values (1,335.52 copies/mL) than those found in immunosuppressed patients with onco-haematological diseases (125,983 copies/mL) (25), chronic kidney disease (2,562.58 copies/ mL) (29) and HIV (501,187 copies/mL) (9).…”

“…Some recent studies have shown that Torque Teno Virus (TTV) is an endogenous marker of immune function, and consequently, the degree of immunosuppression in solid-organ-transplant patients ( 8 ). Both blood and saliva showed high viral loads of TTV in immunosuppressed individuals, in which assessment of saliva represents a non-invasive means of evaluating the immunological state of the patient ( 9 ).…”

“…TTV is not known causes disease in healthy individuals and the viral load is increased in immunosuppressed patients with autoimmune or inflammatory diseases ( 10 ). Recent studies have identified the feasibility of using TTV to monitor the immune state of HIV patients ( 9 ), may be helpful for predicting the occurrence of severe nosocomial infections and mortality in patients with severe COVID-19 ( 12 ), predict graft outcomes in patients after solid organ transplantation and hematopoietic stem cell transplantation ( 13 ), predict clinical deterioration in intensive care unit patients ( 14 ), monitor immunosuppressed patients with rheumatoid arthritis who are on biological disease-modifying anti-rheumatic drugs ( 15 ) and indicate pulmonary function and severity of the disease in chronic obstructive pulmonary disease patients ( 16 ).…”

Impact of polymorphisms in genes orchestrating innate immune responses on replication kinetics of Torque teno virus after kidney transplantation

“…There is increasing evidence on the usefulness of TTV as a surrogate marker of the immune status in a variety of clinical scenarios ( Martin-Lopez et al, 2020 ; Honorato et al, 2021 ; Studenic et al, 2021 ), in particular SOT ( Fernandez-Ruiz et al, 2019 ; Redondo et al, 2022a ; Eldar-Yedidia et al, 2022 ; Jaksch et al, 2022 ), under the rationale that the T-cell-mediated immunity plays an instrumental role in controlling viral replication. Nevertheless, the relative contribution of the innate system—and its genetic determinants—has not been characterized so far.…”

Phylogenetic analysis of torque teno virus in Romania: possible evidence of distinct geographical distribution

“…In the last few years, attention shifted from the pathogenic potential of TTV to its potential use as a biomarker. There is strong evidence supporting the use of TTV DNA-aemia as biomarker for monitoring the kinetics of functional immune competence before and after solid organ transplantation [ 15 – 17 ], monitoring the efficacy of antiviral treatments in HIV-infected patients [ 18 ], or even predicting clinical outcome in SARS-CoV-2-infected patients [ 19 ]. However, discriminating between TTV isolates that may be associated with pathology and innocuous isolates should not be overlooked, and genotyping and tracking their distribution thus remain an important task.…”