Species-Specific TT Viruses and Cross-Species Infection in Nonhuman Primates

Abstract

Viruses resembling human TT virus (TTV) were searched for in sera from nonhuman primates by PCR with primers deduced from well-conserved areas in the untranslated region. TTV DNA was detected in 102 (98%) of 104 chimpanzees, 9 (90%) of 10 Japanese macaques, 4 (100%) of 4 red-bellied tamarins, 5 (83%) of 6 cotton-top tamarins, and 5 (100%) of 5 douroucoulis tested. Analysis of the amplification products of 90 to 106 nucleotides revealed TTV DNA sequences specific for each species, with a decreasing similarity to human TTV in the order of chimpanzee, Japanese macaque, and tamarin/douroucouli TTVs. Full-length viral sequences were amplified by PCR with inverted nested primers deduced from the untranslated region of TTV DNA from each species. All animal TTVs were found to be circular with a genomic length at 3.5 to 3.8 kb, which was comparable to or slightly shorter than human TTV. Sequences closely similar to human TTV were determined by PCR with primers deduced from a coding region (N22 region) and were detected in 49 (47%) of the 104 chimpanzees; they were not found in any animals of the other species. Sequence analysis of the N22 region (222 to 225 nucleotides) of chimpanzee TTV DNAs disclosed four genetic groups that differed by 36.1 to 50.2% from one another; they were 35.0 to 52.8% divergent from any of the 16 genotypes of human TTV. Of the 104 chimpanzees, only 1 was viremic with human TTV of genotype 1a. It was among the 53 chimpanzees which had been used in transmission experiments with human hepatitis viruses. Antibody to TTV of genotype 1a was detected significantly more frequently in the chimpanzees that had been used in transmission experiments than in those that had not (8 of 28 [29%] and 3 of 35 [9%], respectively; P ‫؍‬ 0.038). These results indicate that species-specific TTVs are prevalent in nonhuman primates and that human TTV can cross-infect chimpanzees.

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

“…Human and simian TTVs share closely related genome organization and presumed transcriptional profiles, showing nearly 85% sequence similarity. However, it is now well established that TTV variants in nonhuman primates are species-specific [5,23,24,35,58] and that TTVs from macaques and tamarins are increasingly divergent from TTV variants infecting humans and chimpanzees [35]. Recent evidence shows that simian TTV can infect humans, as it has been observed that approximately 10% of Japanese patients with liver diseases are infected with simian TTV, although the mode of transmission of the infection from animals to humans has not been demonstrated [59].…”

Analysis of the entire genomes of torque teno midi virus variants in chimpanzees: infrequent cross-species infection between humans and chimpanzees

“…We similarly excluded the C-terminal region sequence beyond amino acid 288 as sequences of non-human primates could not be defensibly aligned with each other or with primatederived TTV sequences. The tree showed that chimpanzee TTMDV is a virus species that is phylogenetically distinguishable from TTVs and TTMVs of human and chimpanzee origin as well as TTVs of macaque, douroucouli, tamarin, tupaia, dog, cat and pig, whose entire genomic sequence has thus far been determined (Okamoto et al, 2000a(Okamoto et al, , b, 2001. Of note, chimpanzee TTMDVs were clearly separate from human TTMDVs, while chimpanzee TTVs (Pt-TTV6, s-TTV.CH65-1, s-TTV.CH65-2 and s-TTV.CH71) and chimpanzee TTMV (Pt-TTMV8-II) were interspersed with human TTVs and human TTMVs, respectively.…”

“…Our previous study using a newly developed PCR method revealed high frequencies of viraemia with TTV (99.2 %), TTMDV (82.4 %) and TTMV (89.7 %) among apparently healthy subjects of 1-81 years of age. Additionally, dual or triple infection of these three anelloviruses was seen frequently, even among infants (Ninomiya et al, 2008).Infection with TTV is not restricted to humans; various animal species including non-human primates, tupaias, livestock and some companion animals carry a wide range of highly divergent TTV-like viruses (Inami et al, 2000;Okamoto et al, 2000a Okamoto et al, , b, 2001Okamoto et al, , 2002Thom et al, 2003). Notably, and in contrast with other non-human primates and other animal species, chimpanzees are also infected with TTMVs (Okamoto et al, 2000b).…”

Clinicopathological study on TTV infection in hepatitis of unknown etiology

“…At present, epidemiological studies suggest that TTV is mainly transmitted by blood [13][14][15] ; blood products [16] and body fluid routes [13,17] , it can also be transmitted by mother-to-child vertical [18] and horizontal [19,20] route , fecal-oral route [9,15,21] and sexual route [22] . The infection rate of TTV DNA varies largely in healthy population and patients with liver diseases, but generally, it is higher in patients than in healthy donors [7,[23][24][25][26] . The discovery of TTV once put a light on the etiological diagnoses of hepatitis cases of unknown etiology, unfortunately, the pathogenicity and clinical significance of TTV remain doubtful at this time [25,[27][28][29] .…”

“…TTV is an unenveloped, single-stranded and circular DNA virus, which consists of 3852 nucleotides and most closely resembles the members of the Circoviridae family [1][2][3] . Meanwhile, different studies suggested that TTV genotypes were so much and could vary frequently [4][5][6][7][8] . It is believed that TTV belongs to hepadnavirus and replicates chiefly in the liver [9][10][11] , however, some researchers think that the replication site is in the bone marrows rather than in the livers [12] .…”