Species-Specific TT Viruses in Humans and Nonhuman Primates and Their Phylogenetic Relatedness

Abstract

By means of polymerase chain reaction with a primer pair (NG133-NG147) deduced from the untranslated region (UTR) of TT virus (TTV), TTVs with markedly distinct genomic lengths were recovered from sera of humans and nonhuman primates, and their entire nucleotide sequences were determined. A human TTV [TGP96 of 2908 nucleotides (nt)] was obtained that was about 900 nt shorter than heretofore reported TTVs (3787-3853 nt). Likewise, TTVs of chimpanzee occurred in two distinct genomic sizes [Pt-TTV6 (3690 nt) and Pt-TTV8-II (2785 nt)]. Two TTVs of Japanese macaque [Mf-TTV3 (3798 nt) and Mf-TTV9 (3763 nt)] were comparable in genomic length, but only 55% similar in sequence. These five human and nonhuman primate TTVs, along with TTVs of tamarin [So-TTV2 (3371 nt)] and douroucouli [At-TTV3 (3718 nt)], were compared over the entire nucleotide sequence. Although the seven TTVs were only < or = 55% similar, they share a common genomic organization with two open reading frames (ORFs), designated ORF1 (654-735 amino acids) and ORF2 (91-152 amino acids). The N-terminal sequences of ORF1 proteins were rich in arginine, and sequence motifs necessary for transcription and replication were conserved among them all. Like the human prototype TTV (TA278), all seven TTVs from various animals possessed in common two 15-nt sequences (CGAATGGCTGAGTTT and AGGGGCAATTCGGGC) in the UTR that were covered by NG133 and NG147, respectively. These primers would be instrumental in research on TTVs in previously unexamined species for defining their virological characteristics and evolutionary relationships.

Global impact of Torque teno virus infection in wild and domesticated animals

“…TTV became the prototype of a large group of viral agents with similar genomic organization but a low sequence homology, isolated both in humans and in animals. In fact, in the following years, similar viruses were isolated in other species of vertebrates, including nonhuman primates (chimpanzees, macaques, tamarin monkeys, and douroucouli), pets (dogs and cats), livestock (pigs, cattle, sheep, camels, and poultry), and wild boars, badgers, pine martens, tupaias, rodents, bats, sea turtles, and sea lions [3,5,[23][24][25][26][27][28][29]35]. The natural infection of pigs was first described by Leary et al in 1999 [5]; the first complete genome of Torque teno sus virus (TTSuV) was described by Okamoto in 2002 [3].…”

“…Using conserved UTR-specific primers for detection of TTV DNA, several variants with high genetic diversity have been detected [7,21,32,35,51,52]. Human TTVs belonging to the genus Alphatorquevirus are divided into at least 29 species and more than 40 genotypes and 70 subtypes, with nucleotide differences exceeding 50% among species, more than 30% between genotypes and between 15% and 29% among subtypes.…”

TT virus infection: a novel virus-host relationship

“…1) [16]. From such studies, close to ubiquitous infection with a range of increasingly genetically distinct TTV/TLMV-related viruses has been found in apes, Old World primate species, New World primates, and recently in the tree shrew [17], phylogenetically the most divergent member of the primate order.…”

“…For example, chimpanzees harbour a range of genotypes of TTV and TLMV similar to and frequently interspersed with human genotypes; the existence of homologues of both TTV and TMLV in chimpanzees indicates their evolutionary lineages separated considerably earlier than the 5 million years estimated for host speciation. Old World and New World primates harbour viruses even more divergent than TTV and TLMV, with distinct genome sizes and very little sequence similarity in coding regions [16]. At the furthest extreme, the TTVlike virus detected in the tree shrew shares little but a common genome organisation with viruses from other primates [17].…”

Torque teno sus virus (TTSuV) infection at different stages of pig production cycle

“…This virus was first isolated from a Japanese man with non A-E post-transfusional hepatitis (Nishizawa et al 1997). Since then, TTV has been shown to infect humans, non-human primates, and farm animals (Leary et al 1999, Okamoto et al 2000, 2001, 2002, Brassard et al 2008.…”