Presence Of TT Virus DNA Research Articles

TTV infection in colorectal cancer tissues and normal mucosa

Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg and the Molecular Gastroenterology Unit,Deutsches Krebsforschungszentrum, Heidelberg, GermanyDear Sir,Genetic modifications and environmental factors are presentlyseen as the key factors in the etiology of colorectal cancer,

TT Virus Infection Does Not Affect the Clinical Profiles of Patients with Hepatitis B and C in Yanbian City, China

China is an area of high endemicity for viral hepatitis, and the molecular epidemiological investigation of TT virus (TTV) infection is of interest. In the present study, we investigated the epidemiology, clinical significance and molecular characteristics of TTV infection in patients with chronic hepatitis B and C in Yanbian City, China. Serum samples obtained from 74 patients with hepatitis B and hepatitis C who visited Yanbian Hospital, located in northeast China, were analyzed in this study. The study group included 22 cases of chronic hepatitis B (B-CH), 17 cases of liver cirrhosis B (B-LC), 7 cases of hepatocellular carcinoma (B-HCC), 16 cases of chronic hepatitis C (C-CH), 11 cases of liver cirrhosis C (C-LC) and 1 case of hepatocellular carcinoma (C-HCC). Detection of TTV DNA was performed as described by Nishizawa et al. The second-round PCR products from 7 subjects were sequenced, followed by investigation of nucleotide homology and phylogenetic analysis. TTV DNA was present in 18.2, 5.9, 28.6, 6.3, 9.1 and 0% of the patients with B-CH, B-LC, B-HCC, C-CH, C-LC and C-HCC, respectively. The highest prevalence of TTV infection was seen in the groups aged 40–50 and over 60 years. There was no significant correlation between the presence of TTV DNA and the clinical parameters in patients with hepatitis B and C. The various isolates showed 97.9–100% with isolates reported previously from Japan and 98.4–100% with isolates reported previously from China. Nucleotide sequence analysis revealed that the Yanbian isolates could be classified in the same group as the Japan and China isolates. We concluded that chronic coinfection with TTV did not affect the serological features of chronic hepatitis B and C in China, as found in Tokyo, Japan.

Effect of TT virus co-infection on interferon response in chronic hepatitis C patients.

TT virus (TTV) is a single stranded DNA virus found in serum of patients with post-transfusion non-A to -G hepatitis. TTV-DNA has been investigated in sera of patients with various liver diseases. This study aimed at finding whether co-infection with TTV in HCV patients, may influence the effect of interferon (IFN) in complete elimination of HCV, and analysed the correlation between HCV and TTV by semi-quantification of both HCV RNAs and TTV DNA. In 28 chronic hepatitis C (CH-C) patients with TTV co-infection, the presence of TTV DNA was checked in sera six months before and after the end of IFN therapy. Five out of 28 patients became negative for both HCV-RNA and TTV-DNA following IFN therapy. But 10 out of 28 patients persistently remained positive for both. Among the remaining 13 patients, 5 tested negative for HCV-RNA but positive for TTV-DNA. Post IFN therapy changes in serum alanine aminotransferase (ALT) levels did not appear to be influenced by the presence of TTV co-infection. HCV-RNA was found to be the most important predictor of IFN response in CH-C patients with TTV co-infection. TTV DNA level in sera had no correlation with IFN response. In addition, there was no relationship between HCV RNA and TTV DNA. Based on these results, it can be concluded that the effectiveness of IFN in eliminating HCV does not seem to be influenced by co-infection.

Cloning and sequencing of TT virus genotype 6 and expression of antigenic open reading frame 2 proteins.

The near-full-length genome of a TT virus (TTV) (HEL32), closely related to the previously uncharacterized genotype 6, was cloned and sequenced. The genomic organization of HEL32 was compared to 41 published near-full-length TTV sequences representing 17 genotypes. In the majority of genomes, the open reading frame (ORF) 2 region was divided into two separate ORFs, 2a and 2b. The ORF2a sequence was conserved among all genotypes, while the ORF2b region showed more variability. The two corresponding putative proteins of HEL32 were expressed in prokaryotes and their antigenic potential was studied. IgM and IgG antibodies to the respective ORF2-encoded proteins, fp2a and fp2b, and the presence of TTV DNA were studied in the sera of 89 constitutionally healthy adults. By immunoblot using the small TTV proteins as antigens, strong IgM and IgG reactivities were found in 9 and 10% of subjects, respectively. Follow-up studies for 12-15 years of three subjects showed either a persistent coexistence of IgM and TTV DNA or the appearance of viral DNA regardless of pre-existing antibodies. The low prevalence of IgG could be due to the weak immunogenicity of these probably non-structural proteins or to a genotype-specific antibody response. By nested PCR of the conserved ORF2a region, the prevalence of TTV DNA was 85%. TTV genotype 6 sequences were found by specific PCR in 3 of 35 (8.6%) subjects. The low prevalence of TTV IgG compared to the high TTV DNA prevalence, the coexistence of antibodies and viral DNA and the appearance of TTV DNA regardless of pre-existing antibodies suggest that the B-cell immunity against these minor TTV proteins would not be cross protective.

TT virus detection in oral lichen planus lesions.

Epidemiological studies have demonstrated a correlation between oral lichen planus and different liver diseases. The new virus termed TT virus (TTV) is highly prevalent in patients with chronic hepatitis of different etiology and it may be speculated that TT virus may be involved in the pathogenesis of oral lichen planus. This study examined the presence of TT virus DNA in serum by PCR and in oral mucosa biopsies by in situ hybridization from 20 patients with oral lichen planus (13 with chronic hepatitis and seven without liver disease). Serum and oral mucosa biopsies from six patients all with chronic hepatitis with leukoplakia were also studied as controls. TT virus DNA was positive in the serum of 17/20 (85%) of the patients with oral lichen planus and in all the controls. TT virus DNA hybridization signals were detected in mucosa biopsies from all the patients with TT virus DNA in serum but in none of the three cases without this marker. The percentage of positive cells ranged from 1.6-80%. No differences were found in the percentage of positive cells between TT virus positive patients with and without oral lichen planus and there was no relationship between the number of positive cells and the intensity of the inflammatory infiltrate. In conclusion, TT virus infects oral epithelial cells but the results do not support a role for TT virus in causing oral lichen planus.

Infection with hepatitis A and TT viruses and socioeconomic status in Rio de Janeiro, Brazil.

The prevalence of antibodies directed against the enterically transmitted hepatitis A virus (HAV) was measured in 2 groups of people living in Rio de Janeiro, Brazil. Of 1,056 health care workers (HCWs), 778 (73.7%) were anti-HAV positive. A high prevalence of anti-HAV antibodies (85.7%) was also found among 274 voluntary blood donors (BDs). TT virus (TTV) is a DNA virus that has been found in the sera of patients with post-transfusion hepatitis of unknown etiology. Occurrence of virus shedding suggests that the fecal-oral route may be an important mode of TTV transmission, particularly in the developing world. The presence of TTV DNA was analyzed by PCR in the sera of 191 HCWs and 151 BDs. TTV was detected in 65.4% of HCWs and 79.5% of BDs. In both groups, a family income of < US$400 per month and a level of education of < 11 y of schooling were found to be risk factors for HAV infection. Furthermore, a low family income was associated with TTV viremia in the HCW group. However, the presence of TTV DNA was associated with neither low level of education nor anti-HAV positivity.

Prevalence and viral persistence of TT virus in patients on hemodialysis.

The aim of this study was toevaluate the prevalence of TT virus (TTV) in 107 hemodialysis patients and 100 healthy individuals. Sixteen percent of hemodialysis patients and 2% of the control population were TTV positive (P<0.001). Sex, time on dialysis, transfusions, and alanine aminotransferase levels were not related to the presence of TTV DNA. TTV was more frequent in patients 50 to 70 (12/51) years of age and persisted in the serum of six of nine patients 8 months later. TTV was found in peripheral blood mononuclear cells of all patients with chronic infection, and sequence variation was noted in the peripheral blood mononuclear cells of two patients. No relationship between TTV infection and hepatitis was observed. Viral persistence and nonparenteral transmission may be possible in patients on hemodialysis.

Presence of TTV DNA in serum, liver and peripheral blood mononuclear cells from patients with chronic hepatitis.

The main site of TT virus (TTV) replication remains unknown. Therefore, we have studied the presence and titres of TTV DNA in paired serum, liver and PBMC samples from 50 patients with liver disease (32 with chronic hepatitis B or C, seven with cryptogenic hepatitis and 11 with nonviral liver disease) were included. TTV DNA was analysed by polymerase chain reaction (PCR) using primers from the open reading frame 1 (ORF 1) and from the untranslated region (UTR) and titres were semiquantified by PCR using an external standard. TTV DNA was detected in 26% of serum, 24% of liver and 14% of PBMC samples with ORF 1 primers. When UTR primers were used, 70% of serum and liver samples and 64% of PBMC were TTV DNA positive. No differences between TTV positive and negative patients were found regarding epidemiological or biochemical parameters. Trypsin treatment and fluorescent in situ hybridization confirm the intracellular location of TTV in PBMC. The mean of TTV DNA titres was statistically higher in liver than in serum or PBMC. TTV titres in serum correlated with those in PBMC but not with those in liver. In conclusion, although the liver seems to be the main site for TTV replication, this virus is also able to infect PBMC.

Prevalence of TT virus DNA in eastern Taiwan aborigines.

We studied the prevalence of TT virus (TTV) DNA in the general population of the eastern Taiwan aborigine villages, about 11% (34 of 317). There is no association between the presence of HBsAg and TTV DNA or between the presence of HCV RNA and TTV DNA. Therefore, the infection of HBV or HCV and the presence of TTV DNA appear to be independent from each other. The association between the presence of TTV DNA and the elevated alanine aminotransferase (and/or aspartate aminotransferase) activity was also investigated. The presence of TTV DNA was not found to be correlated with abnormal liver function (P = 0.574) when age, gender, and the presence of HBsAg, HCV RNA, and HGV RNA were all considered in the assay. The sequence homology of TTV DNA fragments between different isolates from Taiwan and N22 (the clone obtained from the original prototype strain) from Japan ranged from 84 to 97%. The recombinant protein encoded by the TTV DNA fragment corresponding to the open reading frame of N22 was expressed in E. coli successfully. However, no serum response against the recombinant protein was detected.

High prevalance of TT virus infection in Japanese patients with liver diseases and in blood donors

Background/Aims: Although a novel DNA virus, TT virus (TTV), has been isolated from a patient with cryptogenic post-transfusion hepatitis, its pathogenic role remains unclear. To elucidate its prevalence and clinical impact in patients with liver diseases, the presence of TTV DNA was assessed in patients with liver diseases and blood donors (BDs) in Japan using two primer sets, one conventional and the other new and highly sensitive. Methods: We studied 261 samples, 72 with chronic hepatitis associated hepatitis C virus (HCV-CH), 57 with hepatocellular carcinoma associated HCV (HCV-HCC), 12 with HCC without either HCV or hepatitis B virus (NBNC-HCC), and 120 of BDs. Results: Using two primer sets, TTV DNA was detected in 68 (94.4%), 53 (93.0%), 12 (100%), and 98 (81.7%) HCV-CH, HCV-HCC, NBNC-HCC, and BDs, respectively. The prevalence was not significantly different between HCV-CH and HCV-HCC, or between HCV-HCC and NBNC-HCC. Comparison between patients with and without TTV revealed no significant differences in backgrounds or biochemical findings. Histopathological findings in patients with HCV-CH, and number, maximum diameter, and histological differentiation of HCC also did not demonstrate any relation to TTV infection. TTV strains can be divided into five groups using phylogenetic analysis, but no disease-specific group appears to exist. Conclusions: Our data suggest that: 1) TTV is very prevalent among patients with liver diseases and even among BDs in Japan, 2) TTV infection does not impact on liver damage with HCV infection, and 3) TTV infection also does not affect the development or progression of HCC.