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1. Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects.

Author

Giacconi R, Maggi F, Macera L, Pistello M, Provinciali M, Giannecchini S, Martelli F, Spezia PG, Mariani E, Galeazzi R, Costarelli L, Iovino L, Galimberti S, Nisi L, Piacenza F, and Malavolta M

Subjects
Aged, Aged, 80 and over, Cause of Death, DNA, Viral blood, Female, Humans, Italy, Kaplan-Meier Estimate, Linear Models, Male, Middle Aged, Viral Load, Immunosenescence, Killer Cells, Natural immunology, MicroRNAs blood, Mortality, Torque teno virus genetics
Abstract

An age-related dysregulation of immune response, known as immunosenescence, contributes to increased susceptibility to infections, frailty and high risk of mortality in the elderly. Torquetenovirus (TTV), a circular, single-stranded DNA virus, is highly prevalent in the general population and it may persist in the organism, also in association with other viruses such as cytomegalovirus (CMV), causing chronic viremia. The relationship that TTV establishes with the immune system of infected hosts is not clear. It is known that TTV encodes microRNAs (miRNAs) that might contribute to immune evasion and that the highest viral loads are found in peripheral blood cells. Moreover, it is suspected that TTV infection lead to increased production of inflammatory mediators, thus playing a role in immunosenescence. We investigated the association of TTV load and miRNAs expression with inflammatory and immune markers and the influence of TTV load on mortality within a cohort of 379 elderly subjects who were followed up for 3 years. TTV DNA load in polymorphonuclear leukocytes was slightly positively correlated with age and negatively associated with serum albumin levels and NK cell activity. A marginal positive correlation between TTV DNA load, monocytes and IL-8 plasma levels was found in females and males respectively. TTV DNA copies ≥4.0 log represented a strong predictor of mortality (Hazard ratio = 4.78, 95% CI: 1.70-13.44, after adjusting for age, sex and the main predictors of mortality rate) and this association remained significant even after the CMV IgG antibody titer was included in the model (HR = 9.83; 95% CI: 2.48-38.97; N = 343 subjects). Moreover, multiple linear regression model showed that TTV miRNA-t3b of genogroup 3 was inversely associated with triglycerides, monocytes and C-reactive protein, and directly associated with IL6. Overall these findings suggest a role of TTV in immunesenescence and in the prediction of all-cause mortality risk in Italian elderly subjects. Further studies are needed to fully understand the pathogenic mechanisms of TTV infection during aging., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2018
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2. Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects

Author

Robertina Giacconi, Roberta Galeazzi, Lisa Macera, Lorenzo Nisi, Francesco Martelli, Francesco Piacenza, Simone Giannecchini, Fabrizio Maggi, Sara Galimberti, Marco Malavolta, Erminia Mariani, Laura Costarelli, Lorenzo Iovino, Mauro Provinciali, Mauro Pistello, Pietro Giorgio Spezia, Giacconi, Robertina, Maggi, Fabrizio, Macera, Lisa, Pistello, Mauro, Provinciali, Mauro, Giannecchini, Simone, Martelli, Francesco, Spezia, Pietro Giorgio, Mariani, Erminia, Galeazzi, Roberta, Costarelli, Laura, Iovino, Lorenzo, Galimberti, Sara, Nisi, Lorenzo, Piacenza, Francesco, and Malavolta, Marco

Subjects
Male, 0301 basic medicine, Aging, Torque teno virus, Immunesenescence, Mortality, NK cell activity, TTV, Biochemistry, Molecular Biology, Genetics, Endocrinology, Cell Biology, Immunosenescence, Population, Viremia, Kaplan-Meier Estimate, 03 medical and health sciences, 0302 clinical medicine, Immune system, Genetic, Cause of Death, medicine, Humans, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Mortality rate, Antibody titer, Middle Aged, Viral Load, medicine.disease, Killer Cells, Natural, MicroRNAs, 030104 developmental biology, Italy, DNA, Viral, Immunology, Linear Models, Female, business, Viral load, 030217 neurology & neurosurgery
Abstract

An age-related dysregulation of immune response, known as immunosenescence, contributes to increased susceptibility to infections, frailty and high risk of mortality in the elderly. Torquetenovirus (TTV), a circular, single-stranded DNA virus, is highly prevalent in the general population and it may persist in the organism, also in association with other viruses such as cytomegalovirus (CMV), causing chronic viremia. The relationship that TTV establishes with the immune system of infected hosts is not clear. It is known that TTV encodes microRNAs (miRNAs) that might contribute to immune evasion and that the highest viral loads are found in peripheral blood cells. Moreover, it is suspected that TTV infection lead to increased production of inflammatory mediators, thus playing a role in immunosenescence. We investigated the association of TTV load and miRNAs expression with inflammatory and immune markers and the influence of TTV load on mortality within a cohort of 379 elderly subjects who were followed up for 3 years. TTV DNA load in polymorphonuclear leukocytes was slightly positively correlated with age and negatively associated with serum albumin levels and NK cell activity. A marginal positive correlation between TTV DNA load, monocytes and IL-8 plasma levels was found in females and males respectively. TTV DNA copies ≥4.0 log represented a strong predictor of mortality (Hazard ratio = 4.78, 95% CI: 1.70-13.44, after adjusting for age, sex and the main predictors of mortality rate) and this association remained significant even after the CMV IgG antibody titer was included in the model (HR = 9.83; 95% CI: 2.48-38.97; N = 343 subjects). Moreover, multiple linear regression model showed that TTV miRNA-t3b of genogroup 3 was inversely associated with triglycerides, monocytes and C-reactive protein, and directly associated with IL6. Overall these findings suggest a role of TTV in immunesenescence and in the prediction of all-cause mortality risk in Italian elderly subjects. Further studies are needed to fully understand the pathogenic mechanisms of TTV infection during aging.

Published
2018

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