TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging
Novazzi, Federica Spezia, Pietro Giorgio Ferrante, Francesca Drago Genoni, Angelo Paolo Grossi, Paolo Antonio Mancini, Nicasio Malavolta, Marco Ballietti, Marta Piacenza, Francesco Marcozzi, Serena
Novazzi, Federica
Spezia, Pietro Giorgio
Ferrante, Francesca Drago
Genoni, Angelo Paolo
Grossi, Paolo Antonio
Mancini, Nicasio
Malavolta, Marco
Ballietti, Marta
Piacenza, Francesco
Marcozzi, Serena
Series / Report no.
Open Access
Type
Journal Article
Article
Article
Language
en
Date of publication
2025-11
Year of publication
Research Projects
Organizational Units
Journal Issue
Title
TTV Species Diversity as a Novel Biomarker of Immune Dysregulation in Aging
Translated Title
Published in
J Med Virol 2025; 97(11):e70656
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.