Characterization of a highly divergent TT virus genome.
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A novel TT virus (TTV)-like DNA sequence was detected in the serum of a patient (PM) with acute non-A-E hepatitis. The full-length genome sequence, referred to here as PM virus (PMV), was obtained and its relationship to other full or near full-length TTV sequences examined. Although it shares a common genomic arrangement and short conserved regions, the majority of the genome is extremely divergent, displaying an average genetic distance of 0.60 from all other TTV sequences. By comparing PMV with TTV genomes representing the most divergent types so far described, six major groups can be distinguished. The level of genetic diversity seen between these genomes is higher than would be expected within a single virus species. Indeed, PMV could be considered the prototype of an independent taxonomic group within the Circoviridae: family. A genoprevalence study of sera from blood donors and patients with acute hepatitis suggests that PMV is rare. (+info)
Three spliced mRNAs of TT virus transcribed from a plasmid containing the entire genome in COS1 cells.
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A permuted whole-genome construct of a TT virus (TTV), named VT416, had 3,852 nucleotides (nt) 98.2% similar to the prototype TA278 genome. To allow the transcription of TTV from the internal promoter, pBK*VT416(1.3G), carrying 1.3 units of VT416, was constructed. The poly(A)(+) RNAs expressed in COS1 cells 48 h posttransfection contained three TTV mRNA species 3.0, 1.2, and 1.0 kb in length, which were recovered in the 13 DNA clones from a lambda phage cDNA library. These mRNAs in the antigenomic orientation possessed in common the 3' terminus downstream of a poly(A) signal (A(3073)ATAAA) and the 5' terminus downstream of a cap site (C(98)ACTTC). A common splicing to join nt 185 with nt 277 was detected in all mRNAs. The coding region of the largest open reading frame (ORF) was maintained in 3.0-kb mRNA, because this splicing was located upstream of its initiation codon (A(589)TG). The second splicing was detected in 1.2-kb mRNA to join nt 711 with nt 2374 and in 1.0-kb mRNA to bind nt 711 to nt 2567. They linked a proposed ORF2 to another ORF for creating new ORFs over nt 2374 to 2872 in frame 2 and nt 2567 to 3074 in frame 3. The donor and acceptor sites of all three splicings matched the consensus sequence and were conserved in most of the 16 TTVs of distinct genotypes retrieved from the database. The observed transcription profile is unique to TTV among known members in the family Circoviridae. (+info)
Sequestration of TT virus of restricted genotypes in peripheral blood mononuclear cells.
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Peripheral blood mononuclear cells (PBMC) harbored TT virus (TTV) of genotypes (3 and 4) different from those (1 and 2) of free virions in plasma of the same individuals. PBMC may act as a reservoir, and TTV of particular genotypes might have tropism for hematopoietic cells. (+info)
Detection rates of TT virus DNA in serum of umbilical cord blood, breast milk and saliva.
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To date, the routes of mother-to-infant transmission of TT virus (TTV) have not been fully elucidated. The present study examines the detection rates of TTV DNA in the serum of pregnant Japanese women and in cord blood at the time of delivery, as well as in the saliva and breast milk of mothers one-month postpartum. Primers derived from the well-known translated region N22 (N22 system), as well as the untranslated region (UTR system) were used. The prevalence of TTV DNA in the serum of pregnant women was found to be 11.9% (19/160) using the N22 system and 72.4% (55/76) using the UTR system. No TTV DNA was detected in the cord blood samples (0/160) when the N22 system was used for detection but TTV DNA was detected in 11.8% (7/76) of samples studied with the UTR system. Using the N22 system, TTV DNA was not detected in breast milk, but was detected in saliva. However using the UTR system, TTV DNA was detected in both specimens. These results imply that some babies are vertically infected with TTV via cord blood at the time of delivery or via breast milk or saliva. However, further research is necessary to confirm this hypothesis. polymerase chain reaction; pregnant women; horizontal route of transmission (+info)
TT virus infection in Japanese children: isolates from genotype 1 are overrepresented in patients with hepatic dysfunction of unknown etiology.
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The pathogenecity of the TT virus (TTV) especially during childhood remains obscure. We investigated the prevalence of TTV in 40 patients with non-A to C hepatic dysfunction (non-A to C hepatic dysfunction group). Five patients with fulminant hepatitis of unknown etiology were enrolled in this group. We also examined 380 children without a history of transfusion or liver disease (control group). Subsequently, the genotypes of TTV strains isolated were analyzed in terms of their nucleotide sequences including 222 bp in the open reading frame 1 region. The prevalence of serum TTV DNA was 10/40 (25%) in the non-A to C hepatic dysfunction group and 25/380 (7%) in the control group. Sixty-six percent (23/35) of all examined cases exhibited either genotype 1 or 2. However, assessment of genotype in the non-A to C hepatic dysfunction group (10 cases) revealed a higher prevalence of genotype 1 than of all other genotypes (80% vs. 20%). This result differed significantly from that of the control group (25 cases; 32% vs. 68%). Such overrepresentation of genotype 1 suggests that this type of TTV strain is associated with the development of hepatic dysfunction of unknown etiology in Japanese children. (+info)
Fecal excretion of a novel human circovirus, TT virus, in healthy children.
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The role of TT virus (TTV) as a human pathogen is unclear, as is the mode of TTV transmission. To determine the prevalence of TTV infection and the possible fecal-oral route of transmission, we analyzed fecal specimens from 67 healthy, nontransfused children for TTV DNA sequences by heminested PCR, using the NG and T primer sets. The overall prevalence of TTV fecal excretion was 22.4% (15 of 67), with the T primer set (19.4%) being more sensitive than the NG primer set (10.4%). TTV prevalence based on gender or ethnicity showed no significant differences. None of seven children in the 0- to 6-month age group had detectable TTV in feces. Of three sets of siblings, two unrelated sets of twins, ages 33 and 37 months, were negative for fecal TTV DNA, while the third set of siblings, ages 99 and 35 months, was positive. The absence of TTV in the feces of children younger than 6 months and the high prevalence (40%) in children 7 to 12 months of age is consistent with age-specific acquisition of TTV infection by the nonparenteral route. TTV genotypes 1, 3, 4, and 5 were represented in our study population. TTV-positive siblings had TTV genotypes 1 and 4, suggesting unrelated environmental sources of TTV infection. This observation suggests a possible time frame for TTV acquisition in children which coincides with increased interaction with their environment and increased susceptibility to infectious agents. (+info)
Full-length nucleotide sequence of a simian TT virus isolate obtained from a chimpanzee: evidence for a new TT virus-like species.
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Recently, we identified TT virus (TTV) isolates from nonhuman primates and named them simian TTV (s-TTV). To characterize the genomic structure of these isolates in more detail, the full-length nucleotide sequence of the s-TTV isolate (designated s-TTV CH65-1), recovered from a chimpanzee born in West Africa, was amplified by nested PCR with inverted primers deduced from the untranslated region of s-TTV DNA. CH65-1 was composed of 3899 nucleotides (nt) and had two open reading frames (ORF) spanning 2295 nt (ORF1) and 402 nt (ORF2). The sequence had only 52.3% similarity to the prototype TA278 human isolate. Phylogenetic analysis demonstrated that CH65-1 was distinct from the human TTV isolates. These results suggested that s-TTV may represent a new TTV-like viral species or genus. (+info)
Species-specific TT viruses in humans and nonhuman primates and their phylogenetic relatedness.
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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. (+info)