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. 2025 Jan 25;26(3):1022.
doi: 10.3390/ijms26031022.

Assessment of Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV) as Complementary Biomarkers to Torquetenovirus (TTV)

Lilia Cinti  1   2   3 , Pietro Giorgio Spezia  4 , Piergiorgio Roberto  1   3   5 , Gianluca Russo  3   6 , Quirino Lai  3   7 , Carolina Carillo  3   8 , Federica Frasca  1   6 , Guido Antonelli  1   3 , Fabrizio Maggi  4
Affiliations

Assessment of Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV) as Complementary Biomarkers to Torquetenovirus (TTV)

Lilia Cinti et al. Int J Mol Sci. .

Abstract

Recent studies have identified Torquetenovirus (TTV) as a promising biomarker of immune competence, particularly in assessing the vaccine response of solid organ transplant (SOT) recipients. However, given the individual variability of viral load, it is not yet possible to define "normal levels". Nevertheless, TTV is just one component of the broader Anelloviridae family, which also includes Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV). This study explores whether the viremia of TTMV and TTMDV offers a stronger predictive marker for vaccine efficacy in SOT recipients. A cohort of 168 SOT patients (142 kidney and 26 lung transplant recipients) who received the BNT162B2 mRNA vaccine was examined, with viral loads quantified through virus-specific real-time PCR. While TTV remains a potentially useful biomarker for evaluating immune response, the combined analysis of all anelloviruses viremia provides deeper insights, particularly in cases where TTV is undetectable. Notably, only TTMV exhibited a pattern similar to TTV, suggesting its potential as an alternative biomarker when TTV is absent from the patient's virome.

Keywords: COVID-19; SOT; Torquetenomidivirus; Torquetenominivirus; Torquetenovirus; anellovirus; biomarker.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Prevalence rates of TTV, TTMV, and TTMDV in the study population.
Figure 2
Figure 2
Co-infection events in the studied population: the y-axis lists the co-infection events, while the x-axis indicates their abundance percentages. (Abbreviations: TTV = Torquetenovirus; TTMV = Torquetenominivirus; TTMDV = Torquetenomidivirus. The “+” sign indicates co-infection between the respective viruses).
Figure 3
Figure 3
The chart illustrates the viral loads for (A) TTV, (B) TTMV, (C) TTMDV, and (D) an overlay of TTV, TTMV, and TTMDV in patients who either responded or did not respond to SARS-CoV-2 vaccination. Medians of the respective viral loads are displayed in all box plots. Statistical significance is indicated as follows: p > 0.05 (NS), p < 0.01 (**), p < 0.001 (***). The exact p-values are as follows: (A) p = [5 × 10−5], (B) p = [4.7 × 10−4], (C): p = [0.12], (D): p = [7 × 10−6].
Figure 4
Figure 4
The diagram highlights linear correlations among: (A) TTMV and TTV, (B) TTMDV and TTV, (C) TTMV and TTMDV. Non-responsive patients to the SARS-CoV-2 vaccine are marked in orange, while seroconverted patients appear in green. The black regression line indicates the correlation level between the viral loads analyzed.
Figure 5
Figure 5
The scatter plot displays the relationship between the viral loads of the three viruses studied, measured in Log copies/mL. Only patients possessing all three viral species are shown. The color scale, as indicated in the legend, represents the TTMDV viral load.
See this image and copyright information in PMC

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