Infection with an unenveloped DNA Virus (TTV) associated with posttransfusion non-A to G hepatitis in hepatitis patients and healthy blood donors in Thailand

Tanaka, Hiroto; Okamoto, Hiroaki; Luengrojanakul, Pairoj; Chainuvati, T; Tsuda, Fumio; Tanaka, Takeshi; Miyakawa, Yuzo; Matsui, Makoto

doi:10.1002/(sici)1096-9071(199811)56:3<234::aid-jmv10>3.0.co;2-e

Cited by 122 publications

(90 citation statements)

References 18 publications

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“…The existence of these three genotypes was subsequently confirmed by several groups of researchers (3,7,10,13,31). TTV genotypes 4, 5, and 6 were recently identified in serum specimens obtained from Asia, Africa, and South America (30).…”

Section: Resultsmentioning

confidence: 77%

“…This observation was later confirmed by other researchers (2,9,15,35) and expanded to identify a third TTV genotype (25). Subsequently, the existence of three TTV genotypes was substantiated by several other groups (3,7,10,13,31). Recently, a phylogenetic analysis performed by using TTV isolates from Asia, Africa, and South America revealed three additional TTV genotypes (30).…”

mentioning

confidence: 64%

“…The other important factor regarding TTV evolution is the capability of multiple genotypes and genetic variants (see above) to persist for a long period in one infected person (3,21,29,31). One study, for example, showed that the nucleotide sequence of TTV genotypes 1 and 2 could be detected over a 15-month follow-up period without any alterations (3).…”

Section: Vol 74 2000mentioning

confidence: 99%

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Sequence Heterogeneity of TT Virus and Closely Related Viruses

Khudyakov

Cong

Nichols

et al. 2000

J Virol

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TT virus (TTV) is a recently discovered infectious agent originally obtained from transfusion-related hepatitis. However, the causative link between the TTV infection and liver disease remains uncertain. Recent studies demonstrated that genome sequences of different TTV strains are significantly divergent. To assess genetic heterogeneity of the TTV genome in more detail, a sequence analysis of PCR fragments (271 bp) amplified from open reading frame 1 (ORF1) was performed. PCR fragments were amplified from 5 to 40% of serum specimens obtained from patients with different forms of hepatitis who reside in different countries (e.g., China, Egypt, Vietnam, and the United States) and from normal human specimens obtained from U.S. residents. A total of 170 PCR fragments were sequenced and compared to sequences derived from the corresponding TTV genome region deposited in GenBank. Genotypes 2 and 3 were found to be significantly more genetically related than any other TTV genotype. Moreover, three sequences were shown to be almost equally related to both genotypes 2 and 3. These observations suggest a merger of genotypes 2 and 3 into one genotype, 2/3. Additionally, five new groups of TTV sequences were identified. One group represents a new genotype, whereas the other four groups were shown to be more evolutionary distant from all known TTV sequences. The evolutionary distances between these four groups were also shown to be greater than between TTV genotypes. The phylogenetic analysis suggested that these four new genetic groups represent closely related yet different viral species. Thus, TTV exists as a "swarm" of at least five closely related but different viruses. These observations suggest a high degree of genetic complexity within the TTV population. The finding of the additional TTV-related species should be taken into consideration when the association between TTV infections and human diseases of unknown etiology is studied.A new TT virus (TTV) was recently discovered in a serum specimen obtained from a Japanese patient with posttransfusion hepatitis of unknown etiology (16,20). In the same study, TTV DNA was detected by PCR in serum specimens from three of five patients with posttransfusion non-A through non-G hepatitis. It was shown that TTV DNA titers closely correlated with the level of aminotransferase in these three patients (16). Additionally, TTV DNA was found in liver tissues in titers that are equal to or 10 to 100 times greater than those in the corresponding serum specimens (20). In combination with these findings, the identification of TTV DNA in 47% of patients with fulminant hepatitis and 46% of patients with chronic liver disease of unknown etiology (20) was used to hypothesize that TTV may be responsible for at least a part of acute and chronic liver disease of unknown etiology (16,20). However, the detection of TTV DNA in 12% of normal blood donors in Japan (20) indicates that this hypothesis should be thoroughly tested before a final conclusion is drawn regarding an association between TTV a...

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Section: Resultsmentioning

confidence: 77%

mentioning

confidence: 64%

Section: Vol 74 2000mentioning

confidence: 99%

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Sequence Heterogeneity of TT Virus and Closely Related Viruses

Khudyakov

Cong

Nichols

et al. 2000

J Virol

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“…TTV and TTLVs demonstrate an extremely wide range of sequence divergence. At least four groups comprising 23 genotypes of TTV have been identified (24,25,34,35,37). In addition, four new genotypes have recently been identified and classified as TTV group 5 (30).…”

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confidence: 99%

Molecular Detection Method for All Known Genotypes of TT Virus (TTV) and TTV-Like Viruses in Thalassemia Patients and Healthy Individuals

Al-Moslih

Ali

et al. 2005

J Clin Microbiol

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High sequence diversity among TT virus (TTV) and TTVlike viruses (TTLVs) is an obstacle to PCR detection of the entire spectrum of existing genotypes. To determine which primers are needed to detect all know genotypes of these viruses, an alignment of commonly used primer sequences with sequences of all known viral genotypes was performed to predict theoretically amplifiable genotypes. The results predicted that all TTV genotypes (except genotype 21), all SEN virus (SENV) genotypes (A to H), and three known TTVL minivirus (TLMV) groups would be detectable by TTV primers NG054/ NG147/133/132 (NG) and TT6/7/8/9 (TT), combined with two TLMV primer sets (TLMV-S and TLMV-L). To confirm these findings, we genetically characterized 420 clones of NG primer products from 32 thalassemia patients and 8 healthy individuals, as well as 50 PCR products amplified by TT and RD037/

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“…This is evident by its excretion in feces [7,15] and in exhaled breath [16]. The association of TTV with cryptogenic chronic liver diseases [17,18], post-transfusion hepatitis [5,11,19] and acute hepatitis of unknown etiology [7], suggested a possible etiological role of this agent in the development of both acute and chronic hepatitis. TTV-DNA has been reported more frequently in patients with liver cirrhosis and hepatocellular carcinoma [20,21], though its role in causing the disease is not known.…”

Section: Introductionmentioning

confidence: 99%

Expression of TTV-ORF2 Protein for Detection of Anti-TTV IgG Antibodies in Human Sera

Singh¹,

Singh²,

Mankotia³

et al. 2013

AID

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The present study describes the cloning and expression of ORF-2 region of TTV genome and the use of expressed peptide in developing immunoassay for detection of anti-TTV antibodies in serum. Presence of TTV-DNA in serum was detected by PCR amplifying N-22 region of ORF-1 of TTV genome. This was followed by genotyping of TTV by RFLP using N-22 amplicon. Using genotype-1 positive serum as the source of TTV, the ORF-2 region was amplified by PCR and subsequently cloned and expressed in pET-19b vector. The expressed protein, identified as 20 kDa protein on SDS-PAGE gel, was purified by affinity chromatography and then used as antigen to develop western blot assay for detection of anti-TTV antibodies in serum. Analysis of sera for anti-TTV antibodies and their comparison with presence of TTV-DNA, produced encouraging results. There was a good relation between presence of anti-TTV and TTV-DNA in these sera samples. Anti-TTV antibodies could be detected in all TTV-DNA positive sera irrespective of the presence of TTV-genotype. This investigation demonstrates that ORF-2 peptide may be used in developing immunoassay for identification of TTV infection.

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Infection with an unenveloped DNA Virus (TTV) associated with posttransfusion non-A to G hepatitis in hepatitis patients and healthy blood donors in Thailand

Cited by 122 publications

References 18 publications

Sequence Heterogeneity of TT Virus and Closely Related Viruses

Sequence Heterogeneity of TT Virus and Closely Related Viruses

Molecular Detection Method for All Known Genotypes of TT Virus (TTV) and TTV-Like Viruses in Thalassemia Patients and Healthy Individuals

Expression of TTV-ORF2 Protein for Detection of Anti-TTV IgG Antibodies in Human Sera

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