Abstract
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 1813 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, cytomegalovirus (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 (odds ratio [OR] = 2.85, 95% confidence interval [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.
Highlights
Torquetenovirus (TTV) is a highly prevalent, nonpathogenic circular single-stranded DNA virus and represents the most abundant component of the human virome [1]
Males with ≥4log TTV copies/ml had a higher risk of having a CD4/CD8 ratio
No differences were found in the examined laboratory parameters such as red blood cell number, hemoglobin, white blood cell count, number of neutrophils, lymphocytes, monocytes and platelets, albumin, C-reactive protein (CRP), fibrinogen, lipid serum levels, fasting glucose, hemoglobin A1c (HbA1c), creatinine, BUN, and CMV IgG antibody titer
Summary
Torquetenovirus (TTV) is a highly prevalent, nonpathogenic circular single-stranded DNA virus and represents the most abundant component of the human virome [1]. Its circulating levels may be related to the status of the immune system, as TTV load increases with age and is associated with a decreased natural killer activity as well as with an increased risk of mortality in the elderly population [2]. It is not yet clear whether TTV can play a direct pathogenic role, the virus might aggravate the course of some diseases [3,4,5] through an increased stimulation of the inflammatory response [6].
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