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Virions are non-enveloped, with reported diameters of about 30 nm for torque teno viruses (TTVs, genus Alphatorquevirus) and torque teno mini viruses (TTMVs, genus Betatorquevirus) (Figure 1).
The buoyant density of virions in CsCl is 1.31–1.33 g cm−3 for TTVs and 1.27–1.28 g cm−3 for TTMVs, both estimated using virus purified from serum.
Virions contain a single molecule of circular ssDNA, which ranges from about 2 to about 3.9 kb in size. Genomes are of negative sense. The putative non-coding region generally contains one or two sequences of about 80–110 nt with high G+C content (ca. 90%), which is postulated to form a secondary structure composed of stems and loops. A region of about 130 nt, located in the untranslated part of the genome, is relatively well conserved between members of the family.
Two main open reading frames, ORF1 and ORF2, and additional ORFs, may be deduced directly from the nucleotide sequence. These ORFs overlap partially, and their estimated sizes differ widely among isolates. Transfection approaches, restricted to the study of some TTV isolates, have demonstrated that at least 5–7 proteins ranging from about 12 to 80 kDa may be expressed via alternative translational initiation. The ORF1 proteins of human and animal anelloviruses possess arginine-rich, hydrophilic N-terminal sequences, and at least one amino acid sequence motif with which rolling circle replication (RCR) of the virus DNA may be associated. On this basis, ORF1 is believed to encode the putative capsid protein and replication-associated protein of anelloviruses. Hypotheses regarding functions of the other proteins are based on studies involving specific isolates. ORF2, which presents a highly conserved motif, WX7HX3CXCX5H, identifiable in its N-terminal part, may encode a protein with phosphatase activity (TTMVs), or a peptide able to suppress NF-κB pathways (TTVs). ORF3 of TTVs has a serine-rich domain at the C-terminus capable of generating different phosphorylation sites, and might play some role in maintaining persistent viral infection. It was also demonstrated that a short TTV peptide, encoded by the N-terminus of a putative ORF, is able to induce p53-independent apoptosis in human hepatocellular carcinoma cell lines.
Anelloviruses harbour a relatively well conserved genetic organization with a coding region containing a major ORF, ORF1, an overlapping ORF2 and several additional ORFs, and an untranslated region (Figure 2). Knowledge of the genome expression and replication mechanisms remains limited, mainly owing to the lack of an efficient cell culture propagation system. TTV-specific mRNAs have been detected in various tissues and organs in humans, and following transfection studies. At least theree mRNAs of different sizes (ca. 2.9, 1.2 and 1.0 kb) are transcribed from the negative strand of the putative circular ds replicative form TTV DNA. The existence of these mRNAs supports the view that both ORF1 and ORF2 are functional, and also suggests that additional transcripts are generated by complex splicing. The transcription profile of other members of the family is not known, but the fact that they share similar genome organizations is highly suggestive that several mRNAs may be expressed as for TTVs. The presence within ORF1 of conserved amino acid sequence motifs, which occur in the Rep proteins of other animal and plant viruses with circular ssDNA genomes (within Circoviridae and Nanoviridae), suggests that replication of anellovirus DNA may use a rolling circle mechanism of replication.
It has been demonstrated that TTV particles in the blood are bound to immunoglobulins G (IgG) and M (IgM), forming immune complexes; they exist as free virions in feces.
Epidemiological studies have demonstrated the global distribution of anelloviruses in rural and urban populations. Their overall prevalence in the general population is high (>90%). Although they were initially suspected of being transmitted only by blood transfusion, the global dispersion of the viruses in populations and their detection in various biological samples (e.g. plasma, saliva and feces) suggests combined modes of diffusion, and in particular the spread by saliva droplets. Other modes of transmission, such as those involving maternal or sexual routes, have also been suggested. The link between anellovirus infection and a specific pathology remains unproven, although some studies suggested possible associations with liver or respiratory diseases, hematological disorders or cancer. The effects of anelloviruses on the immune system are also generally unknown.
Infection with anelloviruses is not restricted to human hosts. Viruses have been detected in non-human primates (chimpanzee, macaque, tamarin and douroucouli), tupaia, pets (cat and dog) and farm animals (pig and cow). Such identifications were recently extended to a marine mammal (sea lion). The analysis of complete viral sequences from different animal sources reveals a high heterogeneity in the size of the viral genome (ca. 2 to 3.9 kb), along with a high genetic divergence when compared with human isolates. However, genomic organization and predicted transcription profiles correspond to those found in human isolates.
Type species Torque teno virus 1
The genus contains viruses identified in humans and non-human primates, with genomes ranging from about 3.6 to 3.9 kb.
Based on analysis of ORF1 in its entirety, a cut-off value of 35% nucleotide sequence identity is applied as a demarcation criterion.
Torque teno virus 1
Torque teno virus 1-TA278
Torque teno virus 2
Torque teno virus 2-CH71
Torque teno virus 3
Torque teno virus 3-HEL32
Torque teno virus 4
Torque teno virus 4-Pt-TTV6
Torque teno virus 5
Torque teno virus 5-TCHN-C1
Torque teno virus 6
Torque teno virus 6-KAV
Torque teno virus 7
Torque teno virus 7-PMV
Torque teno virus 8
Torque teno virus 8-Kt-08F
Torque teno virus 9
Torque teno virus 9-BM1C-18
Torque teno virus 10
Torque teno virus 10-JT34F
Torque teno virus 11
Torque teno virus 11-TCHN-D1
Torque teno virus 12
Torque teno virus 12-CT44F
Torque teno virus 13
Torque teno virus 13-TCHN-A
Torque teno virus 14
Torque teno virus 14-CH65-1
Torque teno virus 15
Torque teno virus 15-TJN01
Torque teno virus 16
Torque teno virus 16-TUS01
Torque teno virus 17
Torque teno virus 17-SENV-G
Torque teno virus 18
Torque teno virus 18-SENV-C
Torque teno virus 19
Torque teno virus 19-SANBAN
Torque teno virus 20
Torque teno virus 20-SAa-10
Torque teno virus 21
Torque teno virus 21-TCHN-B
Torque teno virus 22
Torque teno virus 22-svi-1
Torque teno virus 23
Torque teno virus 23-CH65-2
Torque teno virus 24
Torque teno virus 24-SAa-01
Torque teno virus 25
Torque teno virus 25-Mf-TTV9
Torque teno virus 26
Torque teno virus 26-Mf-TTV3
Torque teno virus 27
Torque teno virus 27-CT23F
Torque teno virus 28
Torque teno virus 28-CT43F
Torque teno virus 29
Torque teno virus 29-yonKC009
Species names are in italic script; names of isolates are in roman script. Sequence accession numbers [ ] and assigned abbreviations ( ) are also listed.
Type species Torque teno mini virus 1
The genus contains viruses identified in humans and non-human primates, with genomes ranging from about 2.8 to 2.9 kb.
Torque teno mini virus 1
Torque teno mini virus 1-CBD279
Torque teno mini virus 2
Torque teno mini virus 2-NLC023
Torque teno mini virus 3
Torque teno mini virus 3-NLC026
Torque teno mini virus 4
Torque teno mini virus 4-Pt-TTV8-II
Torque teno mini virus 5
Torque teno mini virus 5-TGP96
Torque teno mini virus 6
Torque teno mini virus 6-CBD203
Torque teno mini virus 7
Torque teno mini virus 7-CLC156
Torque teno mini virus 8
Torque teno mini virus 8-PB4TL
Torque teno mini virus 9
Torque teno mini virus 9-NLC030
Torque teno mini virus-LIL-y1
Torque teno mini virus-LIL-y2
Torque teno mini virus-LIL-y3
Type species Torque teno midi virus 1
The genus contains viruses identified in humans and non-human primates, with genomes of about about 3.2 kb. Some isolates harbouring shorter genomes (ca. 2–2.6 kb) have been identified.
Torque teno midi virus 1
Torque teno midi virus 1-MD1-073
Torque teno midi virus 2
Torque teno midi virus 2-MD2-013
Torque teno midi virus-2PoSMA
Torque teno midi virus-6PoSMA
Torque teno midi virus-MDJHem2
Torque teno midi virus-MDJHem3-1
Torque teno midi virus-MDJHem3-2
Torque teno midi virus-MDJHem5
Torque teno midi virus-MDJN2
Torque teno midi virus-MDJN14
Torque teno midi virus-MDJN47
Torque teno midi virus-MDJN51
Torque teno midi virus-MDJN69
Torque teno midi virus-MDJN97
Torque teno midi virus-Pt-TTMDV210
Type species Torque teno tupaia virus
The genus contains virus identified in tupaia.
Torque teno tupaia virus
Torque teno tupaia virus-Tbc-TTV14
Type species Torque teno tamarin virus
The genus contains a virus identified in the cotton-top tamarin.
Torque teno tamarin virus
Torque teno tamarin virus-So-TTV2
Type species Torque teno douroucouli virus
The genus contains virus identified in the douroucouli (owl monkey or night monkey).
Torque teno douroucouli virus
Torque teno douroucouli virus-At-TTV3
Type species Torque teno felis virus
The genus contains viruses identified in the domestic cat.
Torque teno felis virus
Torque teno felis virus-Fc-TTV4
Torque teno felis virus-PRA1
Type species Torque teno canis virus
The genus contains virus identified in the domestic dog.
Torque teno canis virus
Torque teno canis virus-Cf-TTV10
Type species Torque teno sus virus 1
The genus contains viruses identified in the pig.
Torque teno sus virus 1
Torque teno sus virus 1-Sd-TTV31
Torque teno sus virus 2
Torque teno sus virus 2-1p
Torque teno sus virus-2p
Note: The nucleotide sequence of this virus identified in swine presents a degree of sequence divergence compatible with the creation of a distinct genus. However, it has been proposed to classify this virus in the genus Iotatoquevirus until further data have been collected in swine species.
Torque teno zalophus virus – ZcAV
Note: virus identified in California sea lion.
The progressive discovery of highly divergent, complete genomes ranging from about 2 to 4 kb in humans and other animals impairs a reliable phylogenetic and taxonomic analysis of full-length sequences. Based on these considerations, the analysis of the entire ORF1 at the nucleotide level (ORF1-nt) is the most convenient approach. Analysis of the distribution of pairwise comparisons and the corresponding phylogenetic tree (see Figure 3) facilitates identification of the levels of genera and species. Based on the currently available data, a taxonomic classification is proposed with the following cut-off values for sequence divergence: genera >56%, species >35%.
Members of the family Anelloviridae have features in common with Chicken anaemia virus, the type species of genus Gyrovirus, family Circoviridae. Namely:
Anello: from Latin anello, “ring”.
Torque: from Latin torques, “necklace”.
Teno: from Latin tenuis, “thin”.
Mini: from Latin minimus, “small”.
Midi: from Latin medius, “intermediate”.
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Jelcic, I., Hotz-Wagenblatt, A., Hunziker, A., Zur Hausen, H. and de Villiers, E.M. (2004). Isolation of multiple TT virus genotypes from spleen biopsy tissue from a Hodgkin's disease patient: genome reorganization and diversity in the hypervariable region. J. Virol., 78, 7498-7507.
Jones, M.S., Kapoor, A., Lukashov, V.V., Simmonds, P., Hecht, F. and Delwart, E. (2005). New DNA viruses identified in patients with acute viral infection syndrome. J. Virol., 79, 8230-8236.
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Nishizawa, T., Okamoto, H., Konishi, K., Yoshizawa, H., Miyakawa, Y. and Mayumi, M. (1997). A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem. Biophys. Res. Commun., 241, 92-97.
Okamoto, H. (2009). TT viruses in animals. Curr. Top. Microbiol. Immunol., 331, 1-20.
Peng, Y.H., Nishizawa, T., Takahashi, M., Ishikawa, T., Yoshikawa, A. and Okamoto, H. (2002). Analysis of the entire genomes of thirteen TT virus variants classifiable into the fourth and fifth genetic groups, isolated from viremic infants. Arch. Virol., 147, 21-41.
Takahashi, K., Iwasa, Y., Hijikata, M. and Mishiro, S. (2000). Identification of a new human DNA virus (TTV-like mini virus, TLMV) intermediately related to TT virus and chicken anemia virus. Arch. Virol., 145, 979-993.
Biagini, P., Bendinelli, M., Hino, S., Kakkola, L., Mankertz, A., Niel, C., Okamoto, H., Raidal, S., Teo, C.G. and Todd, D.