Prevalence and loads of torquetenovirus (TTV) in the European MARK-AGE Study population

Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1,813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians - GO) and premature (Down syndrome - DS) immunosenescence. The TTV load was positively associated with age, CMV antibody levels and the Cu/Zn ratio, and negatively associated with platelets, total cholesterol and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (randomly recruited age-stratified individuals from the general population) populations. In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with ≥4log TTV copies/ml had a higher risk of having a CD4/CD8 ratio<1 than those with lower viremia (OR = 2.85, 95%CI: 1.06-7.62), as well as reduced CD3+ and CD4+T-cells compared to males with lower replication rates (<4log), even after adjusting for CMV infection. In summary, differences in immune system preservation are reflected in the models of delayed and premature immunosenescence, displaying the best and worst control over TTV replication, respectively. In the general population TTV loads were negatively associated with CD4+ cell counts, with an increased predisposition for an inverted CD4/CD8 ratio for individuals with TTV loads ≥4log copies/ml, thus promoting an immune risk phenotype.