TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging

Torquetenovirus (TTV) is a prevalent virus whose clinical significance remains unclear, potentially linked to immunosenescence. This study examines TTV species in relation to immune impairment, inflammation, and cellular stress response in aging. A subset of recruited age-stratified individuals (RASIG) from the MARK-AGE study was divided into three groups: Cohort 1 A (healthy young adults), Cohort 1B (older adults with mild immune decline), and Cohort 1 C (older adults with marked immune impairment). Analyses included TTV load, species diversity, lymphocyte subpopulations, inflammatory markers, Poly-(ADP-ribose) polymerase (PARP-1) expression/activity. Alpha- and beta-diversity analyses showed the highest TTV species diversity in Cohort 1 C, with significant cohort-dependent differences and partially cohort-specific clustering patterns. Increased TTV species number correlated with higher TTV load, elevated CMV IgG levels, and greater immune impairment risk. Specific TTV species were associated with CD4/CD8, and reduced T-cell receptor excision circles, suggesting impaired T-cell homeostasis. TTV viremia positively correlated with C-reactive protein (CRP) and α2-macroglobulin. PARP-1 expression and activity increased in individuals with higher TTV diversity, particularly in the presence of TTV9 and TTV20. TTV load and species diversity are associated with immunosenescence, inflammation, and PARP-1 activation suggesting their potential as biomarkers of age-related immune decline. Longitudinal studies are needed to clarify underlying mechanisms.

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Publication Details

Journal
Journal of Medical Virology
Published
2025-10-23
DOI
https://doi.org/10.1002/jmv.70656
Citations
2
Primary Topic
Animal Virus Infections Studies
Type
article
Field-Weighted Citation Impact
2.39
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article

TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging

Paolo Grossi, Marco Malavolta, Wolfgang Stuetz, Laura Cianfruglia et al.
2 citations
Journal of Medical Virology
Animal Virus Infections Studies
2.39
article

TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging

Paolo Grossi, Marco Malavolta, Wolfgang Stuetz, Laura Cianfruglia, Efstathios S. Gonos, Alexander Bürkle, Angelo Genoni, Francesco Piacenza, Nicasio Mancini, Martijn E.T. Dollé, Pietro Giorgio Spezia, Michele Zampieri, Robertina Giacconi, Mikko Hurme, Fabrizio Maggi, Birgit Weinberger, Fabio Ciccarone, Olivieri Fabiola, Anna Reale, Florence Debacq‐Chainiaux, Eugène Jansen, Carlo Fortunato, Paola Caiafa, Ewa Sikora, Miriam Capri, Serena Marcozzi, Gretta Veronica Badillo Pazmay, María Moreno‐Villanueva, P. Eline Slagboom, Federica Novazzi, Francesca Drago Ferrante, Claudio Franceschi, Tilman Grune, Fabio Filippini, Jürgen Bernhardt, Marta Ballietti
article en
2 citations

Abstract

Torquetenovirus (TTV) is a prevalent virus whose clinical significance remains unclear, potentially linked to immunosenescence. This study examines TTV species in relation to immune impairment, inflammation, and cellular stress response in aging. A subset of recruited age-stratified individuals (RASIG) from the MARK-AGE study was divided into three groups: Cohort 1 A (healthy young adults), Cohort 1B (older adults with mild immune decline), and Cohort 1 C (older adults with marked immune impairment). Analyses included TTV load, species diversity, lymphocyte subpopulations, inflammatory markers, Poly-(ADP-ribose) polymerase (PARP-1) expression/activity. Alpha- and beta-diversity analyses showed the highest TTV species diversity in Cohort 1 C, with significant cohort-dependent differences and partially cohort-specific clustering patterns. Increased TTV species number correlated with higher TTV load, elevated CMV IgG levels, and greater immune impairment risk. Specific TTV species were associated with CD4/CD8, and reduced T-cell receptor excision circles, suggesting impaired T-cell homeostasis. TTV viremia positively correlated with C-reactive protein (CRP) and α2-macroglobulin. PARP-1 expression and activity increased in individuals with higher TTV diversity, particularly in the presence of TTV9 and TTV20. TTV load and species diversity are associated with immunosenescence, inflammation, and PARP-1 activation suggesting their potential as biomarkers of age-related immune decline. Longitudinal studies are needed to clarify underlying mechanisms.

Journal of Medical VirologyVol. 97(11)
University of Pisa (IT), University of Hohenheim (DE), University of Insubria (IT), University of Rome Tor Vergata (IT), Marche Polytechnic University (IT), University of Namur (BE), Vita-Salute San Raffaele University (IT), Tampere University (FI), Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL), University of Konstanz (DE), Universität Innsbruck (AT), Leiden University Medical Center (NL), Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT), National Institute for Public Health and the Environment (NL), Ospedali Riuniti di Ancona (IT), BioTeSys (Germany) (DE), National Hellenic Research Foundation (GR), IRCCS Ospedale San Raffaele (IT), Fondazione Audiologica Varese (IT), Istituto Nazionale di Riposo e Cura per Anziani (IT), German Institute of Human Nutrition (DE), Aziende Socio Sanitarie Territoriale dei Sette Laghi, N. I. Lobachevsky State University of Nizhny Novgorod (RU), Sapienza University of Rome (IT), University of Bologna (IT), HTWG Hochschule Konstanz - Technik, Wirtschaft und Gestaltung (DE), Polish Academy of Sciences (PL)
Openalex Percentile: Top 11%
Animal Virus Infections Studies
2.39
DOIOpen Access PDFOpenAlex
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