Circular Double-Stranded Forms of TT Virus DNA in the Liver

Okamoto, Hiroaki; Ukita, Masato; Nishizawa, Tsutomu; Kishimoto, Junichi; Hoshi, Yuji; Mizuo, Hitoshi; Tanaka, Takeshi; Miyakawa, Yuzo; Mayumi, Makoto

doi:10.1128/jvi.74.11.5161-5167.2000

Cited by 91 publications

(70 citation statements)

References 35 publications

(58 reference statements)

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“…Polarity and single-stranded nature of STTV1. The polarity of the STTV1 genome was determined using the strand-specific primer extension method (51). Purified virus DNA was amplified linearly for 50 cycles with either the STTV1-d sense primer or the STTV1-d antisense primer (Table 1) in a reaction mixture of 50 l. The strand-specific primer extension was repeated with the same primer for an additional 50 cycles by adding the entire first reaction mixture to a new 50-l PCR.…”

Section: Methodsmentioning

confidence: 99%

Discovery of a Novel Single-Stranded DNA Virus from a Sea Turtle Fibropapilloma by Using Viral Metagenomics

Manire

Borrowman

et al. 2009

J Virol

122

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Viral metagenomics, consisting of viral particle purification and shotgun sequencing, is a powerful technique for discovering viruses associated with diseases with no definitive etiology, viruses that share limited homology with known viruses, or viruses that are not culturable. Here we used viral metagenomics to examine viruses associated with sea turtle fibropapillomatosis (FP), a debilitating neoplastic disease affecting sea turtles worldwide. By means of purifying and shotgun sequencing the viral community directly from the fibropapilloma of a Florida green sea turtle, a novel single-stranded DNA virus, sea turtle tornovirus 1 (STTV1), was discovered. The single-stranded, circular genome of STTV1 was approximately 1,800 nucleotides in length. STTV1 has only weak amino acid level identities (25%) to chicken anemia virus in short regions of its genome; hence, STTV1 may represent the first member of a novel virus family. A total of 35 healthy turtles and 27 turtles with FP were tested for STTV1 using PCR, and only 2 turtles severely afflicted with FP were positive. The affected turtles were systemically infected with STTV1, since STTV1 was found in blood and all major organs. STTV1 exists as a quasispecies, with several genome variants identified in the fibropapilloma of each positive turtle, suggesting rapid evolution of this virus. The STTV1 variants were identical over the majority of their genomes but contained a hypervariable region with extensive divergence. This study demonstrates the potential of viral metagenomics for discovering novel viruses directly from animal tissue, which can enhance our understanding of viral evolution and diversity.

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Section: Methodsmentioning

confidence: 99%

Discovery of a Novel Single-Stranded DNA Virus from a Sea Turtle Fibropapilloma by Using Viral Metagenomics

Manire

Borrowman

et al. 2009

J Virol

122

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“…The TT virus is an unenveloped, singlestranded, circular DNA virus with a total genomic length of approximately 3.6-3.9 kilobases that infects human beings worldwide (9). The International Committee on Taxonomy of Viruses has officially named the TT virus as Torque teno virus (TTV) and classified it into a novel family, Anelloviridae (10).…”

Section: Introductionmentioning

confidence: 99%

Serum Torque Teno Virus DNA Titer in Idiopathic Pulmonary Fibrosis Patients with Acute Respiratory Worsening

et al. 2015

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Objective Acute respiratory worsening is defined as the unexpected rapid deterioration of idiopathic pulmonary fibrosis (IPF), and idiopathic acute respiratory worsening is known as an acute exacerbation of IPF. Torque teno virus (TTV) is a circular single-stranded DNA virus whose pathological significance remains unclear. The aim of the present study was to investigate the prevalence and titer of TTV DNA in IPF patients with acute respiratory worsening. Methods The serum TTV DNA titer was measured using real-time PCR in nine IPF patients (two treated with steroids and immunosuppressants; seven treated without steroids or immunosuppressants) who developed acute worsening, including five patients with acute exacerbation. The serum TTV DNA titer was also measured in eight stable IPF cases and four IPF cases of lung cancer. In addition, in order to examine time course changes in the TTV DNA titer, the titer was measured more than once, with an interval of four weeks or longer, in eight patients. Results Among the nine IPF patients with acute worsening, the TTV DNA titer was above 1×10 6 copies/ mL in two subjects without acute exacerbation who had been continuously treated with steroids and immunosuppressants. Meanwhile, the mean TTV DNA titer was 2.4±2.6 (×10 4 copies/mL) in the five patients with acute exacerbation and 3.1±3.4 (×10 4 copies/mL) in the eight patients with stable IPF. Moreover, the TTV DNA titers were increased in all three IPF patients who started treatment with steroids and immunosuppressants. Conclusion Our results suggest that it is unlikely that TTV is directly involved in the onset of acute exacerbation of IPF and that the serum TTV DNA titer potentially reflects the immunosuppressive state of the host due to treatment.

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“…TTV was once regarded as a particular hepadnavirus [36] , but some studies suggested that TTV DNA could be detected in the bone marrows and the peripheral blood mononuclear cells (PBMC), and the hepatocytes were not the only site where TTV infected and existed [11,12] . In our study, we screened the paired tissues of liver, pancreas, kidney, spleen and heart by PCR using doubt-strand probes and P37 probes.…”

Section: Discussionmentioning

confidence: 99%

“…Okamoto et al [11] discovered that separated by gel electrophoresis and characterized biophysically, TTV DNA in sera migrated in sizes ranging from 2.0 to 2.5kb. However, TTV DNA in liver tissues migrated at 2.0 to 2.5kb as well as at 3.5 to 6.1kb.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, different studies suggested that TTV genotypes were so much and could vary frequently [4][5][6][7][8] . It is believed that TTV belongs to hepadnavirus and replicates chiefly in the liver [9][10][11] , however, some researchers think that the replication site is in the bone marrows rather than in the livers [12] . At present, epidemiological studies suggest that TTV is mainly transmitted by blood [13][14][15] ; blood products [16] and body fluid routes [13,17] , it can also be transmitted by mother-to-child vertical [18] and horizontal [19,20] route , fecal-oral route [9,15,21] and sexual route [22] .…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathological study on TTV infection in hepatitis of unknown etiology

Hu¹,

Lang²,

Zhou³

et al. 2002

WJG

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To investigate the state of infection, replication site, pathogenicity and clinical significance of transfusion transmitted virus (TTV) in patients with hepatitis, especially in patients of unknown etiology. METHODS:Liver tissues taken from 136 cases of non-A non-G hepatitis were tested for TT virus antigen and nucleic acid by in situ hybridization (ISH) and nested-polymerase chain reaction (PCR). Among them, TT virus genome and its complemental strand were also detected in 24 cases of autopsy liver and extrahepatic tissues with ISH. Meanwhile, TTV DNA was detected in the sera of 187 hepatitis patients by nested-PCR. The pathological and clinical data of the cases infected with TTV only were analyzed. RESULTS:In liver, the total positive rate of TTV DNA was 32.4% and the positive signals were located in the nuclei of hepatocytes. In serus, TTV DNA was detected in 21.4% cases of hepatitis A-G, 34.4% of non-A non-G hepatitis and 15% of healthy donors. The correspondence rate of TTV DNA detection between liver tissue with ISH and sera with PCR was 63.2% and 89.3% in the same liver tissues by ISH and by PCR, respectively. Using double-strand probes and single-strand probes designed to detect TTV genome, the correspondence rate of TTV DNA detected in liver and extrahepatic tissues was 85.7%. Using singlestrand probes, TTV genome could be detected in liver and extrahepatic tissues by PCR, but its complemental strands (replication strands) could be observed only in livers. The liver function of most cases infected with TTV alone was abnormal and the liver tissues had different pathological damage such as ballooning, acidophilia degeneration, formation of apoptosis bodies and focus of necrosis, but the inflammation in the lobule and portal area was mild. CONCLUSION:The positive rate of TTV DNA among cases of hepatitis was higher than that of donors, especially in patients with non-A non-G hepatitis, but most of them were coinfected with other hepatitis viruses. TTV can infect not only hepatocytes, but also extrahepatic tissues. However, the chief replication place may be liver. The infection of TTV may have some pathogenicity. Although the pathogenicity is comparatively weak, it can still damage the liver tissues.The lesions in acute hepatitis (AH) and chronic hepatitis (CH) are mild, but in severe hepatitis (SH) , it can be very serious and cause liver function failure, therefore, we should pay more attention to TTV when studying the possible pathogens of so-called "liver hepatitis of unknown etiology".

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Circular Double-Stranded Forms of TT Virus DNA in the Liver

Cited by 91 publications

References 35 publications

Discovery of a Novel Single-Stranded DNA Virus from a Sea Turtle Fibropapilloma by Using Viral Metagenomics

Discovery of a Novel Single-Stranded DNA Virus from a Sea Turtle Fibropapilloma by Using Viral Metagenomics

Serum Torque Teno Virus DNA Titer in Idiopathic Pulmonary Fibrosis Patients with Acute Respiratory Worsening

Clinicopathological study on TTV infection in hepatitis of unknown etiology

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