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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)103-111
Number of pages9
JournalExperimental Gerontology
Volume112
DOIs
Publication statusPublished - Oct 2 2018

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MicroRNAs
Viruses
Mortality
DNA
Cytomegalovirus
Immune system
Single-Stranded DNA
Monocytes
Linear Models
Interleukin-8
Linear regression
Serum Albumin
C-Reactive Protein
Infection
Interleukin-6
Hazards
Triglycerides
Blood
Immune Evasion
Immunoglobulin G

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Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects. / 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; Malavolta, Marco.

In: Experimental Gerontology, Vol. 112, 02.10.2018, p. 103-111.

Research output: Contribution to journalArticle

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 ; Malavolta, Marco. / Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects. In: Experimental Gerontology. 2018 ; Vol. 112. pp. 103-111.
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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.",
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T1 - Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects

AU - Giacconi, Robertina

AU - Maggi, Fabrizio

AU - Macera, Lisa

AU - Pistello, Mauro

AU - Provinciali, Mauro

AU - Giannecchini, Simone

AU - Martelli, Francesco

AU - Spezia, Pietro Giorgio

AU - Mariani, Erminia

AU - Galeazzi, Roberta

AU - Costarelli, Laura

AU - Iovino, Lorenzo

AU - Galimberti, Sara

AU - Nisi, Lorenzo

AU - Piacenza, Francesco

AU - Malavolta, Marco

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/10/2

Y1 - 2018/10/2

N2 - 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.

AB - 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.

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M3 - Article

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JO - Experimental Gerontology

JF - Experimental Gerontology

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