# Torque Teno Virus Levels During Viral Respiratory Infections: The Interplay With Immune Dysregulation and Coagulopathy Biomarkers

**Authors:** Roberto Ferrarese, Pietro Giorgio Spezia, Sara Boutahar, Angelo Paolo Genoni, Gabriele Arcari, Gaia Zambon, Maria Dolci, Sara D'alessandro, Giuseppe Sberna, Serena Delbue, Nicasio Mancini, Fabrizio Maggi, Lucia Signorini, Federica Novazzi

PMC · DOI: 10.1002/jmv.70831 · Journal of Medical Virology · 2026-02-07

## TL;DR

This study explores how Torque Teno Virus levels relate to immune and coagulation biomarkers during respiratory viral infections, suggesting it could be a noninvasive marker for immune dysregulation.

## Contribution

The study reveals age-specific immune correlations with TTV levels, offering new insights into immune and coagulation dynamics during respiratory viral infections.

## Key findings

- TTV DNA was detectable across all age groups and viral etiologies, with higher levels in infants and elderly patients.
- Blood and respiratory TTV levels were strongly correlated, indicating a systemic immune response.
- Age-specific immune correlations suggest TTV reflects immune activation and dysregulation during infections.

## Abstract

Torque teno virus (TTV) is a ubiquitous, nonenveloped DNA virus of the Anelloviridae family and a proposed surrogate marker of immune competence. Although nonpathogenic, its replication reflects host immune status and is associated with immune dysregulation during respiratory viral infections (RVIs). This study evaluated the interplay among TTV levels, inflammatory, endothelial, and coagulation biomarkers in acute RVIs. We collected 468 leftover material samples (234 respiratory and 234 blood samples) from hospitalized patients with PCR‐confirmed RVIs. Patients were stratified by viral etiology, differential involvement of the respiratory tract, age, and possible co‐detected pathogens. Cytokines (IL‐6, IL‐8, IL‐1β, TNF‐α), IFNs (α/β/γ), and endothelial markers (ICAM‐1, VCAM‐1) were quantified using microfluidic immunoassays. Routine coagulation parameters were measured in a subset of patients. TTV DNA load was quantified in both compartments using real‐time PCR. Associations with inflammatory and coagulation parameters were assessed using nonparametric tests. TTV DNA was detectable across all age groups and viral etiologies, with higher levels in infants (0–1 years) and elderly patients (81–94 years). Blood and respiratory TTV levels were strongly correlated (r = 0.53, p < 0.0001). In infants, blood TTV correlated positively with IL‐6 and CRP; in elderly patients, inverse correlations with TNF‐α, IFN‐α, and ICAM‐1 suggested less regulated antiviral and endothelial responses. No significant differences were found by viral type or possible co‐detected pathogens, though cytokine–TTV associations persisted. TTV levels reflect systemic and local immune activation during RVIs and deserve further investigation as possible noninvasive biomarker of immune dysregulation and thromboinflammatory risk. Longitudinal studies are needed to determine its prognostic value.

## Linked entities

- **Proteins:** IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), IL1B (interleukin 1 beta), TNF (tumor necrosis factor), IFN1@ (interferon, type 1, cluster), IFNB1 (interferon beta 1), IFNG (interferon gamma), ICAM1 (intercellular adhesion molecule 1), VCAM1 (vascular cell adhesion molecule 1)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ZMYND10 (zinc finger MYND-type containing 10) [NCBI Gene 51364] {aka BLU, CILD22, DNAAF7, FLU}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}
- **Diseases:** Immune Dysregulation (OMIM:614878), systemic (MESH:D015619), bacterial (MESH:D001424), inflammation (MESH:D007249), acute infection (MESH:D000208), thrombotic (MESH:D013927), microvascular dysfunction (MESH:D017566), Infection (MESH:D007239), Endothelial dysfunction (MESH:D014652), COVID-19 (MESH:D000086382), Coagulopathy (MESH:D001778), viral infection (MESH:D014777), respiratory infections (MESH:D012141), influenza (MESH:D007251)
- **Chemicals:** afternucleic acid (-), EDTA (MESH:D004492)
- **Species:** Legionella pneumophila (species) [taxon 446], Human coronavirus NL63 (no rank) [taxon 277944], Enterovirus (genus) [taxon 12059], Streptococcus pneumoniae (species) [taxon 1313], Human immunodeficiency virus 1 (no rank) [taxon 11676], Plataspidae sp. IV1 (species) [taxon 1315218], Respiratory syncytial virus (no rank) [taxon 12814], Human rhinovirus sp. (species) [taxon 169066], Chlamydia pneumoniae (species) [taxon 83558], Mycoplasmoides pneumoniae (Filterable agent of primary atypical pneumonia, species) [taxon 2104], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Human coronavirus 229E (no rank) [taxon 11137], Human enterovirus (species) [taxon 1193974], Haemophilus influenzae (species) [taxon 727], Orthomyxoviridae (family) [taxon 11308], Bordetella pertussis (species) [taxon 520], Torque teno virus (species) [taxon 68887], Metapneumovirus (genus) [taxon 162387], Homo sapiens (human, species) [taxon 9606], Bordetella parapertussis (species) [taxon 519], Bocaparvovirus (genus) [taxon 1507401], PIV 2 [taxon 1979160]
- **Mutations:** (K) in 19-59

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12882057/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC12882057/full.md

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Source: https://tomesphere.com/paper/PMC12882057