Sequence variability in the putative coding region of TT virus: evidence for two rather than several major types.

Abstract

Recently a new human virus, TT virus (TTV) was identified in the serum of a patient with posttransfusion hepatitis of unknown aetiology. Comparative sequence analysis of a 222 nt fragment of ORF1 of TTV was performed to assess the genomic variability of this virus. Phylogenetic analysis of the nucleotide sequences of 76 TTV isolates collected in 17 countries segregated them into two major groups : TTV 1 and TTV 2. The TTV 1 group comprised two distinct subgroups, which corresponded to previously described TTV subtypes 1a and 1b. The TTV 2 group was separated into four main branches, two of which included sequences previously provisionally attributed as TTV types 2 and 3. Bootstrap resampling, however, did not support the reliability of this grouping, suggesting that the isolates in the TTV 2 group should be considered as subtypes of a single type rather than different TTV types.Recently, a novel human infectious agent was identified in a serum sample of a Japanese patient with post-transfusion hepatitis of unknown aetiology (Nishizawa et al., 1997 ;Okamoto et al., 1998). This agent was designated TT virus (TTV), after the name of the patient. The TTV genome is a single-stranded DNA of at least 3739 bases and contains two overlapping open reading frames (ORF1 and ORF2), encoding 770 and 202 amino acids, correspondingly. TTV is resistant to Tween 80 treatment and has a buoyant density of 1n26 g\ml in Author for correspondence : Sergei Viazov (at University of Essen).Fax j49 201 723 5929. e-mail sergei.viazov!uni-essen.deThe GenBank accession numbers of the sequences reported in this paper are AF067973-AF067984, AF081078-AF081087 and AF084105-AF084137. a sucrose gradient. Viral DNA can be detected in plasma but also in liver tissues of infected subjects, suggesting that TTV is hepatotropic. No serological tests for TTV infection markers are available and PCR is at present the only available diagnostic tool. Use of PCR has demonstrated that TTV causes both acute and persistent infections in humans but the epidemiology and clinical significance of these infections remain uncertain. TTV can be transmitted parenterally by blood and blood products (Nishizawa et al., 1997 ;Okamoto et al., 1998 ; Simmonds et al., 1998) and probably also non-parenterally by a faecal-oral route . TTV DNA is present in a large proportion of patients with different forms of non-A-G hepatitis. For example, it was detected in 47 % of patients with fulminant hepatitis and 46 % of patients with chronic liver disease of unknown aetiology in Japan (Nishizawa et al., 1997 ;Okamoto et al., 1998), in 19 % of patients with fulminant hepatic failure from Scotland (Simmonds et al., 1998), and in 25 % of patients with chronic liver disease from England (Naoumov et al., 1998). Of importance is the fact that in the last study the majority of TTV-positive patients had no biochemical or histological evidence of significant liver damage. This finding, as well as the data on the presence of TTV DNA in a surprisingly high proportion (1n9-63 %) of evidently hea...

A case-control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma

“…A total of 15 TTV isolates, including N22 clone 1 and 2 complete coding sequences from Japan (TA278) 2 and China (CHN1) of subtype 1a, are shown for comparative purposes. 14,15 HEPATOLOGY Vol. 30, No.…”

“…8,16 Eleven samples, including 1 of our HCC cases, BsHCC30, form heterogeneous groups, including the TTV sequences formerly belonging to groups G2, G4, G5, and G6. 15,17 Some considerations should be made on the possible route of transmission of TTV. An association between HCV infection and the presence of TTV DNA was found in one study.…”

“…1,2,8,14,15 Primer sequences were derived from the published gene sequences after multiple sequence alignment using the Pile Up program of GCG (Fig. 1).…”

“…Type-specific primer TR 242 was designed after alignment of TTV G2 sequences collected worldwide 1,2,8,[14][15][16][17] (Fig.2). Its specificity was checked by direct sequence analysis of nested PCR products of 224 bp (nt 1939 to 2162).…”

“…For phylogenetic analysis, 23 sequences, 222 nt long (the last two 3Ј nt were removed), taken from 13 HCC cases (BsHCC) and 10 controls (BsCO), were compared together with 44 TTV sequences of the same length, sampled from GenBank. [1][2][14][15][16][17] The whole set of 67 sequences was resampled by bootstrapping 1,000 times and then analyzed using the PHYLIP, v.3.5c, package. 18 Sequence divergence was estimated by the Kimura 2-parameter method, with a transition-transversion ratio of 2:0.…”