Methylation patterns associated with TTV load in geriatric hospitalized patients: an exploratory functional analysis

Torque Teno Virus (TTV) is a widespread commensal virus within the human virome, characterized by a high prevalence in human population and an unclear pathogenic role. Over the past three decades, TTV has garnered increasing attention due to its ability to establish lifelong chronic viremia, which intriguingly fluctuates among individuals in relation to immune competence status, with a typical peak after an organ transplantation, followed by a plateau and a slow decrease. The regulatory mechanisms underlying TTV infection remain elusive, and factors influencing its interactions with the immune system have yet to be identified. To explore this complex interplay, we analyzed DNA methylation patterns associated with TTV load in older adult hospitalized patients (mean age: 83.15 ± 7.49) from the PROMOTERA cohort. In this study, we present for the first time the identification of differentially methylated probes (DMPs) correlated to TTV load in our cohort. The statistically significant DMPs were located in genes involved in immune regulation and lipid metabolism. To further characterize these findings, we performed an exploratory enrichment analysis by applying several p-value thresholds, which yielded multiple gene lists derived from the sets of significant probes. Genes associated with this epigenetic signature were found to enrich functional pathways related to immune activation, leukocyte differentiation, and cytokine production, while additional significantly enriched gene sets were involved in cell-cell adhesion and cell migration processes. Since our analysis followed an exploratory approach, these results should be interpreted as hypothesis-generating and warrant further investigation.

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Publication Details

Journal
GeroScience
Published
2025-10-22
DOI
https://doi.org/10.1007/s11357-025-01938-6
Citations
1
Primary Topic
Animal Virus Infections Studies
Type
article
Field-Weighted Citation Impact
1.19
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article

Methylation patterns associated with TTV load in geriatric hospitalized patients: an exploratory functional analysis

Riccardo Sarzani, Anna Rita Bonfigli, Maurizio Cardelli, Mirko Di Rosa et al.
1 citations
GeroScience
Animal Virus Infections Studies
1.19
article

Methylation patterns associated with TTV load in geriatric hospitalized patients: an exploratory functional analysis

Riccardo Sarzani, Anna Rita Bonfigli, Maurizio Cardelli, Mirko Di Rosa, Paolo Grossi, Fabrizia Lattanzio, Marco Malavolta, Antonio Cherubini, Roberta Galeazzi, Laura Cianfruglia, Francesco Piacenza, Nicasio Mancini, Leonardo Biscetti, Pietro Giorgio Spezia, Robertina Giacconi, Fabrizio Maggi, Olivieri Fabiola, Carlo Fortunato, Davide Gentilini, Gretta Veronica Badillo Pazmay, Federica Novazzi, Francesca Drago Ferrante, Luciano Calzari, L. La Rosa
article en
1 citations

Abstract

Torque Teno Virus (TTV) is a widespread commensal virus within the human virome, characterized by a high prevalence in human population and an unclear pathogenic role. Over the past three decades, TTV has garnered increasing attention due to its ability to establish lifelong chronic viremia, which intriguingly fluctuates among individuals in relation to immune competence status, with a typical peak after an organ transplantation, followed by a plateau and a slow decrease. The regulatory mechanisms underlying TTV infection remain elusive, and factors influencing its interactions with the immune system have yet to be identified. To explore this complex interplay, we analyzed DNA methylation patterns associated with TTV load in older adult hospitalized patients (mean age: 83.15 ± 7.49) from the PROMOTERA cohort. In this study, we present for the first time the identification of differentially methylated probes (DMPs) correlated to TTV load in our cohort. The statistically significant DMPs were located in genes involved in immune regulation and lipid metabolism. To further characterize these findings, we performed an exploratory enrichment analysis by applying several p-value thresholds, which yielded multiple gene lists derived from the sets of significant probes. Genes associated with this epigenetic signature were found to enrich functional pathways related to immune activation, leukocyte differentiation, and cytokine production, while additional significantly enriched gene sets were involved in cell-cell adhesion and cell migration processes. Since our analysis followed an exploratory approach, these results should be interpreted as hypothesis-generating and warrant further investigation.

GeroScience
University of Insubria (IT), Marche Polytechnic University (IT), University of Pavia (IT), European Society of Hypertension (IT), Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT), IRCCS Istituto Auxologico Italiano (IT), Fondazione Audiologica Varese (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Istituto Nazionale di Riposo e Cura per Anziani (IT), Aziende Socio Sanitarie Territoriale dei Sette Laghi
Openalex Percentile: Top 19%
Animal Virus Infections Studies
1.19
DOIOpen Access PDFOpenAlex
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