1887

Abstract

TT virus (TTV), isolated initially from a Japanese patient with hepatitis of unknown aetiology, has since been found to infect both healthy and diseased individuals and numerous prevalence studies have raised questions about its role in unexplained hepatitis. In order to determine the prevalence of ongoing TTV infection as well as resolved infection, a serological study was performed with a recombinant protein generated from the open reading frame 1 (ORF1) sequence isolated from a French patient infected by TTV. The C-terminal end of the ORF1 protein, containing a particularly hydrophilic region, was retained to be used as antigen to detect the presence of anti-TTV antibodies in serum samples by a Western blot analysis. For this purpose, the C-terminal ORF1 region was expressed in fusion with a hexahistidine tail in and purified by metal-chelate affinity chromatography. The serological screening of 70 human sera, including 30 patients with hepatitis of unknown aetiology, 30 blood donors and 10 healthy children, allowed the immune response of infected hosts to be identified by the detection of TTV-specific antibodies, with a very high prevalence of 98·6% in the human sera tested. In contrast, TTV DNA was detected by PCR in only 76·1% of the tested sera. The use of the ORF1 C-terminal recombinant protein thereby provided a diagnostic tool to follow the immune response of the host against TTV.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-12-2949
2000-12-01
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/12/0812949a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-12-2949&mimeType=html&fmt=ahah

References

  1. Abe, K., Inami, T., Asano, K., Miyoshi, C., Masaki, N., Hayashi, S., Ishikawa, K., Takebe, Y., Win, K. M., El-Zayadi, A. R., Han, K. H. & Zhang, D. Y. ( 1999; ). TT virus infection is widespread in the general populations from different geographic regions. Journal of Clinical Microbiology 37, 2703-2705.
    [Google Scholar]
  2. Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W. & Lipman, D. J. ( 1997; ). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research 25, 3389-3402.[CrossRef]
    [Google Scholar]
  3. Biagini, P., Gallian, P., Attoui, H., Cantaloube, J.-F., de Micco, P. & de Lamballerie, X. ( 1999; ). Determination and phylogenetic analysis of partial sequences from TT virus isolates. Journal of General Virology 80, 419-424.
    [Google Scholar]
  4. Charlton, M., Adjei, P., Poterucha, J., Zein, N., Moore, B., Therneau, T., Krom, R. & Wiesner, R. ( 1998; ). TT-virus infection in North American blood donors, patients with fulminant hepatic failure, and cryptogenic cirrhosis. Hepatology 28, 839-842.[CrossRef]
    [Google Scholar]
  5. Desai, S. M., Muerhoff, A. S., Leary, T. P., Erker, J. C., Simons, J. N., Chalmers, M. L., Birkenmeyer, L. G., Pilot-Matias, T. J. & Mushahwar, I. K. ( 1999; ). Prevalence of TT virus infection in US blood donors and populations at risk for acquiring parenterally transmitted viruses. Journal of Infectious Diseases 179, 1242-1244.[CrossRef]
    [Google Scholar]
  6. Erker, J. C., Leary, T. P., Desai, S. M., Chalmers, M. L. & Mushahwar, I. K. ( 1999; ). Analyses of TT virus full-length genomic sequences. Journal of General Virology 80, 1743-1750.
    [Google Scholar]
  7. Fukuda, Y., Nakano, I., Katano, Y., Kumada, T., Hayashi, K., Nakano, S. & Hayakawa, T. ( 1999; ). TT virus (TTV) is not associated with acute sporadic hepatitis. Infection 27, 125-127.[CrossRef]
    [Google Scholar]
  8. Hijikata, M., Takahashi, K. & Mishiro, S. ( 1999; ). Complete circular DNA genome of a TT virus variant (isolate name SANBAN) and 44 partial ORF2 sequences implicating a great degree of diversity beyond genotypes. Virology 260, 17-22.[CrossRef]
    [Google Scholar]
  9. Höhne, M., Berg, T., Müller, A. R. & Schreier, E. ( 1998; ). Detection of sequences of TT virus, a novel DNA virus, in German patients. Journal of General Virology 79, 2761-2764.
    [Google Scholar]
  10. Hopp, T. P. & Woods, K. R. ( 1981; ). Prediction of protein antigenic determinants from amino acid sequences. Proceedings of the National Academy of Sciences, USA 78, 3824-3828.[CrossRef]
    [Google Scholar]
  11. Hsieh, S. Y., Wu, Y. H., Ho, Y. P., Tsao, K. C., Yeh, C. T. & Liaw, Y. F. ( 1999; ). High prevalence of TT virus infection in healthy children and adults and in patients with liver disease in Taiwan. Journal of Clinical Microbiology 37, 1829-1831.
    [Google Scholar]
  12. Irving, W. L., Ball, J. K., Berridge, S., Curran, R., Grabowska, A. M., Jameson, C. L., Neal, K. R., Ryder, S. D. & Thomson, B. J. ( 1999; ). TT virus infection in patients with hepatitis C: frequency, persistence, and sequence heterogeneity. Journal of Infectious Diseases 180, 27-34.[CrossRef]
    [Google Scholar]
  13. Laemmli, U. K. ( 1970; ). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.[CrossRef]
    [Google Scholar]
  14. Leary, T. P., Erker, J. C., Chalmers, M. L., Desai, S. M. & Mushahwar, I. K. ( 1999; ). Improved detection systems for TT virus reveal high prevalence in humans, non-human primates and farm animals. Journal of General Virology 80, 2115-2120.
    [Google Scholar]
  15. Li, W. H. ( 1993; ). Unbiased estimation of the rates of synonymous and nonsynonymous substitution. Journal of Molecular Evolution 36, 96-99.[CrossRef]
    [Google Scholar]
  16. Maggi, F., Fornai, C., Morrica, A., Casula, F., Vatteroni, M. L., Marchi, S., Ciccorossi, P., Riente, L., Pistello, M. & Bendinelli, M. ( 1999; ). High prevalence of TT virus viremia in Italian patients, regardless of age, clinical diagnosis, and previous interferon treatment. Journal of Infectious Diseases 180, 838-842.[CrossRef]
    [Google Scholar]
  17. Miyata, H., Tsunoda, H., Kazi, A., Yamada, A., Ali Khan, M., Murakami, J., Kamahora, T., Shiraki, K. & Hino, S. ( 1999; ). Identification of a novel GC-rich 113-nucleotide region to complete the circular, single-stranded DNA genome of TT virus, the first human circovirus. Journal of Virology 73, 3582-3586.
    [Google Scholar]
  18. Mushahwar, I. K., Erker, J. C., Muerhoff, A. S., Leary, T. P., Simons, J. N., Birkenmeyer, L. G., Chalmers, M. L., Pilot-Matias, T. J. & Desai, S. M. ( 1999; ). Molecular and biophysical characterization of TT virus: evidence for a new virus family infecting humans. Proceedings of the National Academy of Sciences, USA 96, 3177-3182.[CrossRef]
    [Google Scholar]
  19. Naoumov, N. V., Petrova, E. P., Thomas, M. G. & Williams, R. ( 1998; ). Presence of a newly described human DNA virus (TTV) in patients with liver disease. Lancet 352, 195-197.[CrossRef]
    [Google Scholar]
  20. Niagro, F. D., Forsthoefel, A. N., Lawther, R. P., Kamalanathan, L., Ritchie, B. W., Latimer, K. S. & Lukert, P. D. ( 1998; ). Beak and feather disease virus and porcine circovirus genomes: intermediates between the geminiviruses and plant circoviruses. Archives of Virology 143, 1723-1744.[CrossRef]
    [Google Scholar]
  21. Nishizawa, T., Okamoto, H., Konishi, K., Yoshizawa, H., Miyakawa, Y. & Mayumi, M. ( 1997; ). A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochemical and Biophysical Research Communications 241, 92-97.[CrossRef]
    [Google Scholar]
  22. Nishizawa, T., Okamoto, H., Tsuda, F., Aikawa, T., Sugai, Y., Konishi, K., Akahane, Y., Ukita, M., Tanaka, T., Miyakawa, Y. & Mayumi, M. ( 1999; ). Quasispecies of TT virus (TTV) with sequence divergence in hypervariable regions of the capsid protein in chronic TTV infection. Journal of Virology 73, 9604-9608.
    [Google Scholar]
  23. Okamoto, H., Nishizawa, T., Kato, N., Ukita, M., Ikeda, H., Iizuka, H., Miyakawa, Y. & Mayumi, M. ( 1998a; ). Molecular cloning and characterization of a novel DNA virus (TTV) associated with posttransfusion hepatitis of unknown etiology. Hepatology Research 10, 1-16.[CrossRef]
    [Google Scholar]
  24. Okamoto, H., Akahane, Y., Ukita, M., Fukuda, M., Tsuda, F., Miyakawa, Y. & Mayumi, M. ( 1998b; ). Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A–G hepatitis. Journal of Medical Virology 56, 128-132.[CrossRef]
    [Google Scholar]
  25. Okamoto, H., Nishizawa, T., Ukita, M., Takahashi, M., Fukuda, M., Iizuka, H., Miyakawa, Y. & Mayumi, M. ( 1999a; ). The entire nucleotide sequence of a TT virus isolate from the United States (TUS01): comparison with reported isolates and phylogenetic analysis. Virology 259, 437-448.[CrossRef]
    [Google Scholar]
  26. Okamoto, H., Takahashi, M., Nishizawa, T., Ukita, M., Fukuda, M., Tsuda, F., Miyakawa, Y. & Mayumi, M. ( 1999b; ). Marked genomic heterogeneity and frequent mixed infection of TT virus demonstrated by PCR with primers from coding and noncoding regions. Virology 259, 428-436.[CrossRef]
    [Google Scholar]
  27. Prescott, L. E. & Simmonds, P. ( 1998; ). Global distribution of transfusion-transmitted virus. New England Journal of Medicine 339, 776-777.[CrossRef]
    [Google Scholar]
  28. Saback, F. L., Gomes, S. A., de Paula, V. S., da Silva, R. R. S., Lewis-Ximenez, L. L. & Niel, C. ( 1999; ). Age-specific prevalence and transmission of TT virus. Journal of Medical Virology 59, 318-322.[CrossRef]
    [Google Scholar]
  29. Saitou, N. & Nei, M. ( 1987; ). The neighbor-joining method: a new method for constructing phylogenetic trees. Molecular Biology and Evolution 4, 406-425.
    [Google Scholar]
  30. Simmonds, P., Davidson, F., Lycett, C., Prescott, L. E., MacDonald, D. M., Ellender, J., Yap, P. L., Ludlam, C. A., Haydon, G. H., Gillon, J. & Jarvis, L. M. ( 1998; ). Detection of a novel DNA virus (TTV) in blood donors and blood products. Lancet 352, 191-195.[CrossRef]
    [Google Scholar]
  31. Sugiyama, K., Goto, K., Ando, T., Mizutani, F., Terabe, K., Kawabe, Y. & Wada, Y. ( 1999; ). Route of TT virus infection in children. Journal of Medical Virology 59, 204-207.[CrossRef]
    [Google Scholar]
  32. Takahashi, K., Ohta, Y. & Mishiro, S. ( 1998a; ). Partial 2·4-kb sequences of TT virus (TTV) genome from eight Japanese isolates: diagnostic and phylogenetic implications. Hepatology Research 12, 111-120.[CrossRef]
    [Google Scholar]
  33. Takahashi, K., Hoshino, H., Ohta, Y., Yoshida, N. & Mishiro, S. ( 1998b; ). Very high prevalence of TT virus (TTV) infection in the general population of Japan revealed by a new set of PCR primers. Hepatology Research 12, 233-239.[CrossRef]
    [Google Scholar]
  34. Tanaka, H., Okamoto, H., Luengrojanakul, P., Chainuvati, T., Tsuda, F., Tanaka, T., Miyakawa, Y. & Mayumi, M. ( 1998; ). Infection with an unenveloped DNA virus (TTV) associated with posttransfusion non-A to G hepatitis in hepatitis patients and healthy blood donors in Thailand. Journal of Medical Virology 56, 234-238.[CrossRef]
    [Google Scholar]
  35. Thompson, J. D., Higgins, D. G. & Gibson, T. J. ( 1994; ). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research 22, 4673-4680.[CrossRef]
    [Google Scholar]
  36. Towbin, H., Staehelin, T. & Gordon, J. ( 1979; ). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences, USA 76, 4350-4354.[CrossRef]
    [Google Scholar]
  37. Tsuda, F., Okamoto, H., Ukita, M., Tanaka, T., Akahane, Y., Konishi, K., Yoshizawa, H., Miyakawa, Y. & Mayumi, M. ( 1999; ). Determination of antibodies to TT virus (TTV) and application to blood donors and patients with post-transfusion non-A to G hepatitis in Japan. Journal of Virological Methods 77, 199-206.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-12-2949
Loading
/content/journal/jgv/10.1099/0022-1317-81-12-2949
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error