Identification of a new genotype of Torque Teno Mini virus

Abstract

Background: Although human torque teno viruses (TTVs) were first discovered in 1997, still many associated aspects are not clarified yet. The viruses reveal a remarkable heterogeneity and it is possible that some genotypes are more pathogenic than others. The identification of all genotypes is essential to confirm previous pathogenicity data, and an unbiased search for novel viruses is needed to identify TTVs that might be related to disease.

Method: The virus discovery technique VIDISCA-454 was used to screen serum of 55 HIV-1 positive injecting drug users, from the Amsterdam Cohort Studies, in search for novel blood-blood transmittable viruses which are undetectable via normal diagnostics or panvirus-primer PCRs.

Results: A novel torque teno mini virus (TTMV) was identified in two patients and the sequence of the full genomes were determined. The virus is significantly different from the known TTMVs (< 40% amino acid identity in ORF1), yet it contains conserved characteristics that are also present in other TTMVs. The virus is chronically present in both patients, and these patients both suffered from a pneumococcal pneumonia during follow up and had extremely low B-cells counts.

Conclusion: We describe a novel TTMV which we tentatively named TTMV-13. Further research is needed to address the epidemiology and pathogenicity of this novel virus.

Figure 1

Genomic organization of the new TTMV genotype. Arrows represent ORFs, and the box indicates the GC-rich region. Putative proteins sizes for each ORF are given in amino acids: The ORF1 encodes a 662 amino acid long putative capsid protein, ORF2 and ORF3 a 94 and 126 amino acid putative protein, respectively. Conserved motifs in TTVs are indicated.

Figure 2

TTMV phylogeny derived from ORF1 amino acid sequences. ORF1 amino acid sequences (662 amino acids) of known TTMVs were aligned with TTMV-13 and phylogenetically analyzed. Numbers at nodes indicate bootstrap support (1000 replicates). The scale bar is a measure of the proportion of divergence. LogL = −20869.57.

Figure 3

Follow up data of patient D50 (A) and D11 (B) infected by the new genotype of TTMV. On the X-axis the time of follow up in the Amsterdam Cohort Studies is shown, the cell counts (cells/mm³) on the left Y-axis and the concentration of the TTMV-13 virus in copies per ml on the right Y-axis. TTMV-13 virus loads below the detection limit (100 copies/ml serum) are indicated as 100 copies/ml.