The discovery of TTMV, like the original Torque Teno virus (TTV) isolate, was accidental. After TTV was isolated in 1997 from a Japanese patient, primers were created to study TTV in more detail. TTV-specific primers used in PCR of human plasma samples yielded sequences that partially matched that of TTV, but were noticeably shorter.[2][3] TTV was eventually understood to have a genome of 3.6–3.9 kb, while TTMV has a genome of 2.8–2.9 kb. Another TT-like virus later isolated in 2007, Torque teno midi virus or TTMDV, has a genome of 3.2 kb.[3]
Genome and capsid
TTMV shares similar morphologic features with the other human anelloviruses. The capsid has a T=1 icosahedral symmetry.[2] The virion does not have a lipid envelope and is thus "naked", making it an extremely simple virus. It is estimated that the virion is a little less than 30 nm in diameter.[2][3]
The genome is circular and made of single-stranded DNA of negative polarity. It is 2.86–2.91 kilobases long.[2] Anelloviruses are known for having 3 or 4 overlapping, nested open reading frames; TTMV has 3 ORF's that overlap.[2][4] ORF-2 and ORF-3 overlap with ORF-1 at opposite ends. For TTMV, ORF-1 is about 663 residues and ORF-2 is about 91 residues long.[2] There is a highly conserved 130-nt region just downstream of the TATA box.[3]
Phylogeny & spread
TTMV is highly divergent.[2][3] The first phylogenetic tree created from TTMV genomic sequences revealed a large cluster of strains; ORF-1 had divergences of over 42% at the nucleotide level and over 67% at the amino acid level.[2]
TTMV is also highly prevalent, like other human anelloviruses. Subsequent research after it was discovered has yielded the prevalence of TTMV DNA among blood donors to be 48%–72%.[3] It can likely infect a wide range of tissues, as it has been isolated from various body fluids and tissues, including saliva, feces, plasma/serum, PBMCs, bone marrow, spleen, pancreas, kidneys, nervous tissue, lymph nodes, semen, and cervical swabs.[2][3] Its exact transmission mechanism is unknown, but is thought to be possible by blood-borne, sexual, fecal-oral, and respiratory routes.[2]
Recent studies have shown that humans can have multiple infections of TT viruses.[3][4]
Clinical
Though TTVs are potentially associated with diseases and their pathogenicity has been debated since their discovery, TTMV is not currently known as an explicit cause of any human disease.[2] TTMV has been isolated from a number of parapneumonic empyema.[5] However, its clinical significance remains unclear.
^Galmès J, Li Y, Rajoharison A, Ren L, Dollet S, Richard N, Vernet G, Javouhey E, Wang J, Telles JN, Paranhos-Baccalà G (2012) Potential implication of new torque teno mini viruses in parapneumonic empyema in children. Eur Respir J