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The TT virus (TTV) was isolated recently from the serum of a patient with post-transfusion hepatitis. TTV infection is widespread in the general population, and its prevalence increases continuously with age. The pathogenic role of TTV in liver disease remains controversial, and the source of transmission is still unclear. We investigated the pathogenicity and epidemiology of TTV infection in infants born to TTV DNA-positive mothers. Enrolled in this study were 22 mother-child pairs testing negative for antibodies to hepatitis B, hepatitis C, and the human immunodeficiency viruses (HIVs). The children were followed for 30 months after birth. Serum TTV DNA was detected by N22-PCR, and the PCR products were cloned and sequenced. The prevalence of TTV infection in children increased with age. Of the 22 children, 13 (59%) became positive for TTV DNA during the follow-up period. Of these 13 children, 6 (46%) had elevated levels of serum alanine aminotransferase (ALT), although the elevations were transient and mild. TTV viremia was not associated significantly with the abnormal ALT levels. Children with TTV viremia developed neither severe liver disease nor fulminant hepatitis. Phylogenetic analysis showed that, in 11 (85%) of the 13 pairs, the mother and child had the same genotype at the first PCR-positive time point. Among those 11 mother-child pairs, 6 (55%) had identical TTV nucleotide sequences. However, the genotype of predominant clones changed in 5 (50%) of 10 children who were positive for TTV DNA at two or more time points during the follow-up period. In conclusion, this study did not provide evidence that TTV infection is related to liver disease in children. Although the main source of TTV infection in children is presumed to be their mothers, transmitted via non-parenteral routes in the course of daily contact, intrafamilial carriers may also be sources of TTV infection.

Serum samples from healthy and diseased children were studied for the presence of TTV DNA by nested PCR using primer sets generated from N-22 region and from the untranslated region (UTR) of the viral genome. N-22 positive TTV DNA was detectable in 33 (27%) of 122 healthy children, 47 (73.4%) of 64 polytransfused thalassemic children, 37 (46.3%) of 80 children who received transfusion during cardiac surgery, 8 (42.1%) of 19 non-A to E hepatitis, 10 (33.3%) of 30 HBV carrier children, and 5 (15.6%) of 32 infants with biliary atresia. A much higher prevalence of TTV DNA with rates varying from 78-100% in the above study groups was observed using the UTR primers. For children with N-22 positive TTV DNA, biochemical assessment of isolated TTV viremia in thalassemic children or children transfused during surgery showed no convincing association between raised ALT levels and TTV viremia. Coinfection with TTV in chronic HCV-infected or HBV-infected children did not result in higher peak ALT levels during follow-up, suggesting that TTV has no synergistic pathogenic effect. The phylogenetic analysis of the N-22 positive TTV DNA isolates revealed that most isolates from healthy children, children transfused during surgery, and non-A to E fulminant hepatitis children were type 1 TTV. These results indicate that TTV infection in children was significantly associated with transfusion. TTV infection is highly prevalent in early childhood in Taiwan but plays a minimal role in the induction of hepatitis in children., (Copyright 2003 Wiley-Liss, Inc.)

Sera from 30 women at high risk for infection, one half of which were SEN virus positive (SENV(+)), were collected at delivery to study SENV mother-to child transmission. Thirteen of their babies were positive for at least one SENV strain: one baby was SENV(+) at birth, eight became positive within 6 months from delivery, and four became positive in the following months. Our data indicate that vertical transmission of SENV does occur, presumably, at delivery, but it may not induce persistent viremia. This is supported by the fact that, generally, SENV is not detected at birth, by the high SENV homology in the sequences found in the mothers and in their children, by a lack of other risk factors for infection of the babies, and by the irregular detection of SENV in the follow-up. No clinical events surely linked to SENV infection were found, but transient elevations of alanine aminotransferase were observed in babies followed for a long period of time., (Copyright 2002 Wiley-Liss, Inc.)

This study assessed the prevalence of TT virus (TTV) viremia in pregnant women and evaluated the role of maternal transmission in early acquisition of TTV in infants in Taiwan. Two groups of pregnant women were screened for TTV using polymerase chain reaction. The first group included 135 healthy pregnant women attending the obstetrics department for routine prenatal care and the second group from 25 GB virus-C/hepatitis G virus (GBV-C/HGV)-infected mothers. In both groups, when TTV infection was found in mothers, serial serum samples were collected for the infants at regular intervals until 1 year of age and were tested for TTV DNA. The results showed that 40% (54/135) of the women undergoing routine prenatal care and 56% (14/25) of GBV-C/HGV-infected pregnant women were positive for TTV DNA (P = 0.137). Of the 54 TTV-infected mothers in the routine prenatal group, 29 and their 30 infants received regular follow-up. The positive rate of TTV DNA in infants was 40% (12/30) in the routine prenatal group and 29% (4/14) in the group with GBV-C/HGV-infected mothers (P = 0.463). All but 2 of the 16 TTV-infected infants had normal serum alanine aminotransferase levels during follow-up. The phylogenetic analysis in 7 mother-infant pairs showed that the homology was diverse in each pair and a close genetic relatedness was found in 2 mother-infant pairs. In conclusion, TTV viremia is common in pregnant Taiwanese women and their infants. However, the results suggest that maternal transmission may play only a minor role in early acquisition of TTV in infants., (Copyright 2002 Wiley-Liss, Inc.)

Serum TT virus (TTV) DNA was determined in 83 human immunodeficiency virus type 1 (HIV 1) infected mothers [46 intravenous drug user and 37 non-intravenous drug user women] and their infants. Twenty-nine (34.9%) mothers were TTV infected. Infection was more frequent among intravenous drug user than non-intravenous drug user mothers [21/46 (45.6%) vs. 8/37 (21.6%); relative risk (RR): 2.1; 95% confidence limits (95% CL): 1.1-4.2; P = 0.023] and among intravenous drug users who carried on injecting than in those who had given it up [10/14 (71.4%) vs. 11/32 (34.3%); RR: 2.1 (95%CL: 1.2-3.7); P = 0. 021]. Infection was not related to age, CD4-positive T-lymphocyte counts, HIV 1 load, hepatitis B (HBV), G/GB-C (GBV-C/HGV), C (HCV) virus exposure. Eight (27.5%) infants born to TTV infected (but none of those born to TTV uninfected) mothers were TTV infected at a median age of 1.5 (range: 0.6-2.8) months. Infants born by vaginal/emergency caesarean delivery were more frequently infected than those born by elective caesarean delivery [7/16 (43.7%) vs. 1/13 (7.6%); RR: 2.1; 95%CL: 1.2-3.5; P = 0.033]. Infection in infants was not related to maternal CD4-positive T-lymphocyte counts, HIV 1 load, and HIV 1, HBV, GBV-C/HGV, or HCV transmission. No infant became TTV infected thereafter. No TTV infected child [follow-up: 31 (median; range: 6-60) months] showed signs of liver disease; five infants cleared TTV DNA after 22 (median; range: 6-60) months. TTV infection in HIV 1 infected women is prevalently related to intravenous drug user. The findings suggest that infants may acquire TTV at birth. Infection may persist without evident liver disease., (Copyright 2000 Wiley-Liss, Inc.)

Virus fragments homologous to TTV were detected previously from an enterically transmitted outbreak of non-A-E hepatitis [Luo et al., 1999]. To test the susceptibility of the Rhesus monkey to this virus and to establish its transmission routes, 6 Rhesus monkeys were inoculated, 3 orally and another 3 intravenously. The inoculum was prepared by extracting and filtering feces collected from a patient during the incubation period identified in the described outbreak. A second group of 3 monkeys was used for the passage study. The feces and blood samples were collected for detection of the virus by polymerase chain reaction (PCR). Four animals were subjected to liver biopsies and bile aspiration by open surgery for in situ virus detection. Viremia occurred in 4-7 days after intravenous and 7-10 days after oral inoculation. The virus was excreted in feces a few days after oral infection and simultaneously with viremia after intravenous inoculation. The virus was also detected in bile during the viremic phase. There was a prolonged carrier state with persistent viremia and virus excretion in feces for more than 6 months. Serum transaminase levels were not raised during the infection. The virus was present in both the cytoplasm and nuclei of hepatocytes, but no significant pathology was found. Therefore, the Rhesus monkey is susceptible to TT virus infection, but the virus seems nonpathogenic. Infection of the liver may be established either by oral or parenteral inoculation. The virus may be released from liver into the blood or via bile into feces, so it may be transmitted by both blood and fecal routes., (Copyright 2000 Wiley-Liss, Inc.)

TT virus (TTV) is an unenveloped, single-stranded DNA virus that was discovered recently in the sera of Japanese patients with posttransfusion hepatitis of unknown etiology. A high prevalence of TTV infection in blood donors of several countries, including Brazil, has been demonstrated. To study the variation in TTV prevalence between different age groups, sera from 223 individuals without liver disease, aged 0-80 years, were tested by the polymerase chain reaction for the presence of TTV DNA. All subjects were inhabitants of the city of Rio de Janeiro, Brazil. The prevalence increased continuously with age (P <.001), from 17% among children under the age of 11 years, to 57% in people older than 50 years. To assess vertical transmission, sera from 105 unselected, consecutive parturient women attending a public maternity hospital were paired with cord bloods and examined for the presence of TTV DNA. Thirty-seven (35%) mothers were found to be TTV infected. Seven cord bloods were also positive, suggesting the possible transplacental transmission of the virus. Furthermore, a direct correlation between TTV viremia and presence of antibodies to the enterically transmissible hepatitis A virus (HAV) was observed in this group of women, with a relative risk of TTV infection of 5.09 (95% confidence interval 0.76-34.03) for women with anti-HAV, compared with women without. This finding suggested that the fecal-oral route might be an important route of TTV transmission.

Recently, a novel DNA virus, TT virus (TTV), was identified in patients with post-transfusion non-A-G hepatitis. We analyzed the prevalence and clinical implications of TTV infection in a cohort of 96 Spanish patients on long-term hemodialysis. TTV DNA was detected by nested PCR in 51 (53%) of 96 patients, a prevalence significantly higher than that found in healthy blood donors. Persistent liver test abnormalities were found in only 2 (7.7%) of 26 patients infected with TTV alone, compared with 12 (75%) of 16 patients infected with hepatitis C or hepatitis B virus, or both (P < 0.01). Mixed infections with multiple strains of TTV, including different major genotypes, were common in patients on hemodialysis. These patients had received a significantly greater number of blood units (22.7 +/- 20) compared with patients apparently infected with a single strain of TTV (8.9 +/- 11) (P = 0.01). Phylogenetic analyses of TTV from infected patients identified strains of genotypes 1, 2, 3, and 4. In summary, TTV infection was common in patients on hemodialysis but was not associated with liver disease

TT virus (TTV) is a novel viral agent, detected recently in non-A to E hepatitis cases. Little is known about its natural history or routes of transmission in childhood. For the detection of serum TTV DNA, semi-nested polymerase chain reaction (PCR) was carried out using TTV-specific primers and TTV nucleotide sequences were determined by the dideoxy chain-mediated termination method. Five of the 70 children studied (including 20 hepatitis B virus [HBV] carriers, 40 children born to HBV carrier mothers and 10 children born to hepatitis C virus [HCV] carrier mothers) had serum TTV DNA. Three of the 5 children had siblings (4 in total), so that a total of 9 children were studied to determine the time of initial serum TTV DNA detection. In the 8 seropositive children, the time of serum TTV DNA detection ranged from 6 to 14 months after birth, and TTV DNA persisted thereafter throughout the follow-up period. The TTV DNA-negative child was assessed most recently at 6 months of age. TTV DNA was detected in only 2 of the 4 mothers tested (families 2 and 3). When 271-bp TTV DNA fragments from each of the 8 children were sequenced, the degree of homology between siblings in families 1-3 was 100%, 99.5%, and 92.3%, respectively. The degree of homology between child-mother pairs of families 2 and 3 was 99.5-100% and 62. 6-63.9%, respectively. The distribution of different TTV strains was consistent within families, except for family 3. None of the TTV-infected children had elevated levels of alanine aminotransferase or clinical signs of liver disease., (Copyright 1999 Wiley-Liss, Inc.)