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Mother-to-child transmission of TT virus: sequence analysis of non-coding region of TT virus in infected mother-infant pairs

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ARCHIVES OF VIROLOGY 2002年第4期147卷 803-812页

作者： Bagaglio, S Sitia, G Prati, D Cella, D Hasson, H Novati, R Lazzarin, A Morsica, G San Raffaele Sci Inst Dept Infect Dis I-20127 Milan Italy IRCCS Osped Maggiore Ctr Trasfus & Immunol Trapianti Milan Italy San Raffaele Sci Inst Neonatal Unit Dept Pediat Milan Italy

To investigate vertical transmission of TT virus, TTV-dna was looked for in serum samples taken from 22 mothers and their 22 infants at birth and during nine months of follow-up. Sixteen mothers at delivery and six infants within nine months of age had TTV-dna detected by the amplification of the non coding (NC) region. Two of these newborns had positive viremia at birth. Sequence analysis of the NC region of five mother-infant pairs revealed that the TTV strains detected at three and six months of age in two of the infants were closely related to that of their mothers, whereas two that became TTV-dna positive at three moths had a different nucleotide sequence from that of their mothers. One of the two infants with detectable viremia at birth also had a different nucleotide sequence from her mother. These findings suggest that both in utero and perinatal transmission of TT virus may occur, and that the strain detected in the infants was not invariably dominant in the mothers at delivery.

关键词：碱基序列克隆分子 dna病毒感染/传播 dna病毒感染/病毒学传染性疾病传播垂直分子序列数据开放读码框架种系发生前瞻性研究序列比对序列同源性核酸输血传播病毒/分类输血传播病毒/遗传学病毒血症成年人女(雌)性人类婴儿婴儿新生妊娠

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TT virus (TTV) genotypes in native and non-native prostitutes of Irian Jaya, Indonesia: implication for non-occupational transmission

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ARCHIVES OF VIROLOGY 2000年第1期145卷 63-72页

作者： Mulyanto Hijikata, M Matsushita, M Ingkokusmo, G Widjaya, A Sumarsidi, D Kanai, K Ohta, Y Mishiro, S Toshiba Gen Hosp Dept Med Sci Shinagawa Ku Tokyo 1408522 Japan W Nusa Tenggara Hepatitis Lab Mataram Indonesia Univ Mataram Basic Sci Lab Mataram Indonesia Teikyo Univ Sch Med Dept Med 4 Kanagawa Japan Irian Jaya Prov Hlth Off Jaya Pura Indonesia Program Appropriate Technol Hlth Jakarta Indonesia Toshiba Gen Hosp Dept Gastroenterol Tokyo Japan

We investigated prostitutes in Irian Jaya, an Indonesian territory of New Guinea, to know whether TT virus (TTV) is sexually transmitted and what genotypes of TTV exist there. An ORF2 region of the TTV genome was analyzed for 44 isolates from prostitutes (19 were Irian Jaya natives but 25 were immigrants from Java or other islands of Indonesia) and 26 isolates from women of child-bearing age in Surabaya as a control. The WX7HX3CX1CX5H motif sequence of the ORF2 was compared across the 70 Indonesian isolates with a reference of 47 Japanese isolates (filed in databases) and the prototype TTV isolate TA278. A total of 77 different sequences were generated from the comparison, but a phylogenetic analysis suggested that they could be divided into three categories: group Al group B and others (the third group was highly diverse). Interestingly, most of the Indonesian isolates belonged to group B (74%): this rate was considerably higher than that observed previously in Japanese isolates. Group B isolates were further compared for the N-terminal 95 amino acids of the ORF2, with a result that the natives of Irian Jaya had a different pattern of genotype distribution from other groups. In particular, 9 out of 19 isolates from the Irian Jaya-natives were co-classified under a distinct branch, to which none of the other Indonesian and Japanese isolates belonged. Our data indicate that TTV genotypes reflect the birth place of the infected prostitutes rather than their work environment, and thus suggest that an infection is more likely during the early period of life than through sexual transmission. In addition, the presence of an Irian Jaya-specific genotype is intriguing from an anthropological and viral evolutionary point of view, because Irian Jaya has been isolated from contact with other areas for a long time.

关键词：氨基酸序列 dna病毒感染/流行病学 dna病毒感染/传播 dna病毒感染/病毒学 dna病毒/分类 dna病毒/遗传学 dna 病毒/分析 dna 病毒/遗传学基因型肝炎病毒/分类肝炎病毒/遗传学肝炎病毒性人/流行病学肝炎病毒性人/传播肝炎病毒性人/病毒学印度尼西亚/流行病学分子序列数据开放读码框架种系发生卖淫序列分析 dna 病毒蛋白质类/化学病毒蛋白质类/遗传学青少年成年人女(雌)性人类

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Molecular epidemiology of TT virus (TTV) and characterization of two novel TTV genotypes in Indonesia

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ARCHIVES OF VIROLOGY 2001年第7期146卷 1249-1266页

作者： Muljono, DH Nishizawa, T Tsuda, F Takahashi, M Okamoto, H Jichi Med Sch Div Immunol Minami Kawachi Tochigi 3290498 Japan Jichi Med Sch Div Mol Virol Minami Kawachi Tochigi Japan Eijkman Inst Mol Biol Infect Dis Lab Jakarta Indonesia Toshiba Gen Hosp Dept Med Sci Tokyo Japan

The prevalence of TT virus (TTV) dna among 244 healthy individuals in 23 cities on 12 islands in Indonesia was determined by polymerase chain reaction (PCR) with primers derived from the coding region (N22), which can detect TTV dna of genotypes 1-6. By N22 PCR, TTV dna was detected in 102 (42%) individuals. The amplified PCR products were molecularly cloned and three clones each were subjected to sequence analysis. Three hundred one (98%) of the 306 TTV clones were classified into genotype 1, 2 or 3, and none into genotypes 4-6. The remaining five clones from two individuals (Kt-08 and Kt-10) on Kutai, Kalimantan Island, differed by > 30% from known TTV isolates of all 21 genotypes and were tentatively classified into genotypes 22 and 23, respectively. Using primers specific for the new TTV genotype 22 or 23, TTV genotype 22 was detected significantly more frequently in Kutai than in the other 22 cities (41% vs. 5%, P < 0.001). TTV genotype 23 was restricted to Kutai (17% vs. 0%, P < 0.001), suggesting the indigenous nature of this genotype. Analysis of two TTV isolates (Kt-08F and Kt-10F) demonstrated the extreme diversity of TTV and the preservation of the genomic organization and transcription profile.

关键词：克隆分子 dna病毒感染/流行病学 dna病毒感染/病毒学 dna 病毒/遗传学 dna 病毒/分离和提纯进化分子基因型印度尼西亚/流行病学分子流行病学分子序列数据核酸类/分离和提纯开放读码框架种系发生聚合酶链反应/方法序列同源性氨基酸序列同源性核酸输血传播病毒/分类输血传播病毒/遗传学输血传播病毒/分离和提纯成年人女(雌)性人类男(雄)性中年人

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Genotypes of TT virus (TTV) compared between liver disease patients and healthy individuals using a new PCR system capable of differentiating 1a and 1b types from others

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ARCHIVES OF VIROLOGY 1999年第12期144卷 2345-2354页

作者： Hijikata, M Iwata, K Ohta, Y Nakao, K Matsumoto, M Matsumoto, H Kanai, K Baba, K Samokhvalov, EI Mishiro, S Toshiba Gen Hosp Dept Med Sci Shinagawa Ku Tokyo 1408522 Japan Toshiba Gen Hosp Dept Gastroenterol Tokyo 1408522 Japan Toshiba Gen Hosp Cent Clin Lab Tokyo 1408522 Japan Russian Acad Med Sci DI Ivanovskii Virol Inst Moscow Russia

TT virus (TTV) lacks obvious pathogenicity;almost all of the infected hosts are symptom-free. A possibility remains, however, that certain strains can cause liver disease while most others are non-pathogenic. Genotypes 1a and 1b have been proposed to contain such pathogenic strains. To test this possibility, we constructed a PCR system capable of detecting TTV of the 1a and 1b genotypes differentially from the other genotypes, and compared the frequencies of these genotypes between patients with liver disease of unknown etiology (n = 42) and healthy individuals (n = 50). The assay comprised 3 steps: i) PCR to amplify a 3.2-kb fragment using universal primers;ii) 2nd-round PCR, starting from the 3.2-kb amplicon, for a similar to 280-nt fragment by use of genotype 1-specific primers;and iii) digestion of the similar to 280-nt amplicon with MboI and BanI to discriminate between la and Ib. Eventually, 40 (95%) of the patients and 47 (94%) of the controls were positive for the 3.2-kb amplicon, and the 1a, 1b, 1a+1b, and non-1 genotypes of TTV were found in 2 (5%) vs 4 (9%), 5 (13%) vs 4 (9%), 1 (3%) vs 1 (2%) and 32 (80%) vs 38 (81%) of the 40 patients and 47 controls, respectively: the distribution was almost identical between the two groups. The hypothesis that the genotype 1 of TTV may be more closely associated with liver disease than other genotypes was not supported by this study.

关键词：碱基序列病例对照研究 dna引物 dna病毒感染/病毒学 dna病毒/分类 dna病毒/遗传学 dna病毒/致病力 dna 病毒/分离和提纯基因型肝炎病毒性人/病毒学肝疾病/病毒学分子序列数据聚合酶链反应/方法序列分析 dna 人类

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Prevalence and genetic diversity of TT virus genotype 21 (YONBAN virus) in Brazil

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ARCHIVES OF VIROLOGY 2003年第3期148卷 517-529页

作者： Vasconcelos, HCF Gomes, SA Cataldo, M Niel, C Inst Oswaldo Cruz Dept Virol BR-21045900 Rio De Janeiro Brazil Univ Fed Santa Catarina Dept Clin Anal Florianopolis SC Brazil

Isolates of the newly characterized, single-stranded dna virus TTV, have been tentatively classified into four major phylogenetic groups and at least 28 genotypes. Four Japanese isolates, designated as YONBAN viruses, belong to the fourth group and to genotype 21. In this study, a genotype 21-specific PCR assay was standardized. With this assay, 48/184 (26%) serum samples and 76/167 (46%) saliva samples, collected from unselected ambulatory patients (aged 2 to 82) of a Brazilian public hospital, were positive. A total of 110 (66%) patients had TTV genotype 21 dna in serum, saliva, or both fluids. Furthermore, 18/37 (49%) serum samples, collected from Indians belonging to three ethnic groups of the Western Brazilian Amazon, were also positive. Nucleotide sequences (253 bases at the 3' end of the non-coding region of the genome) were determined, that derived from 25 individuals, i.e. 17 patients and eight Indians. Phylogenetic analysis showed that three: isolates from Indians of a :particular ethnic group formed a separate subgroup within genotype 21. Among non-Indians, a clustering of strains was: observed according to their country of origin (Japan or Brazil), with all 17 sequences derived from Brazilian patients located in a unique subgroup.

关键词：门诊医疗巴西/流行病学 dna病毒感染/流行病学 dna病毒感染/人种学 dna病毒感染/病毒学 dna 病毒/分析基因型医院大学印第安人南美洲分子序列数据种系发生患病率序列分析 dna 输血传播病毒/分类输血传播病毒/遗传学输血传播病毒/分离和提纯变异(遗传学) 青少年成年人老年人老年人 80以上儿童儿童学龄前女(雌)性人类男(雄)性中年人

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Clinical implications of TT virus superinfection in patients with chronic hepatitis C

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AMERICAN JOURNAL OF GASTROENTEROLOGY 2000年第7期95卷 1776-1780页

作者： Watanabe, H Saito, T Kawamata, O Shao, L Aoki, M Terui, Y Mitsuhashi, H Matsuo, T Takeda, Y Saito, K Togashi, H Shinzawa, H Takahashi, T Yamagata Univ Sch Med Dept Internal Med 2 Yamagata 9909585 Japan SRL Inc Ctr Mol Biol & Cytogenet Hepatitis Virus Anal Sect Tokyo Japan

OBJECTIVE: TT virus (TTV) has been identified as a candidate agent of non-A-E hepatitis virus. We investigated superinfection of TTV in patients with chronic hepatitis C and studied the susceptibility to interferon (IFN) treatment and its association with liver disease caused by hepatitis C virus (HCV). METHODS: TTV dna was examined using the seminested polymerase chain reaction (PCR), and its virus level was measured by the real-time fluorometric PCR. RESULTS: TTV dna was detected in 20 of 102 (19.6%) patients examined. There was no significant difference in the alanine aminotransferase (ALT) level between patients with or without TTV dna. Quantitative analysis of HCV RNA and TTV dna revealed no correlation between virus levels in HCV/TTV-coinfected patients. Both TTV and HCV were sensitive to IFN therapy. Complete response to IFN with a sustained loss of viremia for 24 wk after completion of IFN treatment was found in 11 of 20 (55%) patients with respect to TTV dna and in five of 20 (25%) patients with respect to HCV RNA. The mean pretreatment HCV RNA level was significantly lower in the complete-response cases than in the no-response cases, but there was no significant difference in the pretreatment TTV dna levels between them. ALT normalization resulting from IFN therapy was not attributable to the eradication of TTV dna but was attributable to that of HCV RNA. Superinfection by TTV did not influence the effect of IFN against HCV. No specific TTV genotype correlating with IFN sensitivity was found. CONCLUSIONS: These results suggest that TTV infection stands independent of HCV infection, with no influence on liver injury as a result of HCV infection. (C) 2000 by Am. Coll. of Gastroenterology).

关键词：抗病毒药/治疗应用 dna病毒感染/并发症 dna病毒感染/药物疗法 dna病毒感染/病毒学 dna病毒/遗传学 dna 病毒/血液基因型肝炎丙型慢性/并发症肝炎丙型慢性/药物疗法肝炎丙型慢性/病毒学干扰素类/治疗应用微生物敏感性试验 RNA 病毒/血液重叠感染青少年成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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