Genomic Diversity of Torque Teno Virus in Blood Samples from Febrile Paediatric Outpatients in Tanzania: A Descriptive Cohort Study

Abstract

Torque teno virus (TTV) is considered to be an ubiquitous member of the commensal human blood virome commonly reported in mixed genotype co-infections. This study investigates the genomic diversity of TTV in blood samples from 816 febrile Tanzanian children. Metagenomic next-generation sequencing was used to screen for TTV in individual blood samples from a cohort of 816 febrile Tanzanian paediatric outpatients. For positive samples, the number of TTV species and genotypes present were evaluated. We investigate the linear relationship between individual TTV diversity and the patient age by linear regression. TTV was detected in 97.2% of sera. ORF1 analysis revealed the presence of 149 genotypes from 38 species, suggesting the presence of 13 new species. These genotypes were mostly present as co-infections with a median of 11 genotypes/subject (range: 1−71). In terms of species, we found a median of nine species/subject (range: 1−29). We further show a significant association between the diversity of co-detected TTV and the age of the subjects (p value < 0.0001). This study shows that significant TTV genomic diversity is acquired by the age of five and that this diversity tends to increase with age, which indicates a repetitive TTV acquisition during the first months/years of life.

Trial registration: ClinicalTrials.gov NCT02225769.

Keywords: children; genomic diversity; torque teno virus.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Flowchart of study and TTV analysis.

Figure 2

Age repartition. Age repartition of the 816 patients enrolled in this mNGS study. Medians are reported by black bars. Unpaired t-test was used to compare means. ns, nonsignificant.

Figure 3

Frequency of each TTV species and genotype. (a) Barplot showing the number of positive patients for each TTV species detected by mNGS. The 25 TTV species known to infect humans as well as the 13 additional species reported in this study are represented by black and grey bars, respectively; (b) Barplot showing the number of positive patients for each TTV genotype detected by mNGS.

Figure 4

TTV genomic diversity in serum. (a) Number of TTV species detected by mNGS for each patient. Median is reported (black bar); (b) Simple linear regression analysis of the number of TTV species and the age of the patients (in months). Each black dot represents one of the 785 positive patients; (c) Number of TTV genotypes detected by mNGS for each patient. Median is reported (black bar); (d) Simple linear regression analysis of the number of TTV genotypes and the age of the patients (month). Each black dot represents one of the 785 positive patients for which a genotype could be obtained (≥50% ORF1).

Figure 5

Relationship between co-detected TTV genotypes within a same patient. Each of the 149 TTV genotypes reported by mNGS in this paediatric cohort is represented by a dot of variable size depending on the number of times (i.e., counts) it is detected. Genotypes are grouped by species, and each of the 38 TTV species reported in this study being represented by a specific colour code. Each line indicates which TTV genotype (dark purple end) is frequently co-detected with which other (light purple end). A co-detection cut-off of ≥75% is used in order to illustrate only strong TTV genotypes co-detection rates.