1887

Abstract

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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-5-979
2002-05-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/5/0830979a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-5-979&mimeType=html&fmt=ahah

References

  1. Ball, J. K., Curran, R., Berridge, S., Grabowska, A. M., Jameson, C. L., Thomson, B. J., Irving, W. L. & Sharp, P. M. ( 1999; ). TT virus sequence heterogeneity in vivo: evidence for co-infection with multiple genetic types. Journal of General Virology 80, 1759-1768.
    [Google Scholar]
  2. Bendinelli, M., Pistello, M., Maggi, F., Fornai, C., Freer, G. & Vatteroni, M. L. ( 2001; ). Molecular properties, biology, and clinical implications of TT virus, a recently identified widespread infectious agent of humans. Clinical Microbiology Reviews 14, 98-113.[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. Douglas, A. J., Phenix, K., Mawhinney, K. A., Todd, D., Mackie, D. P. & Curran, W. L. ( 1995; ). Identification of a 24 kDa protein expressed by chicken anaemia virus. Journal of General Virology 76, 1557-1562.[CrossRef]
    [Google Scholar]
  5. Ellis, S. R., Hopper, A. K. & Martin, N. C. ( 1987; ). Amino-terminal extension generated from an upstream AUG codon is not required for mitochondrial import of yeast N2,N2-dimethylguanosine-specific tRNA methyltransferase. Proceedings of the National Academy of Science, USA 84, 5172-5176.[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. Felsenstein, J. C. ( 1989; ). PHYLIP: Phylogeny Interference Package, version 3.2. Cladistics 5, 164-166.
    [Google Scholar]
  8. Gallian, P., Berland, Y., Olmer, M., Raccah, D., de Micco, P., Biagini, P., Simon, S., Bouchouareb, D., Mourey, C., Roubicek, C., Touinssi, M., Cantaloube, J.-F., Dussol, B. & de Lamballerie, X. ( 1999; ). TT virus infection in French hemodialysis patients: study of prevalence and risk factors. Journal of Clinical Microbiology 37, 2538-2542.
    [Google Scholar]
  9. Gallian, P., Biagini, P., Zhong, S., Touinssi, M., Yeo, W., Cantaloube, F. J., Attoui, H., de Micco, P., Johnson, P. J. & de Lamballerie, X. ( 2000; ). TT virus: a study of molecular epidemiology and transmission of genotypes 1, 2 and 3. Journal of Clinical Virology 17, 43-49.[CrossRef]
    [Google Scholar]
  10. Handa, A., Dickstein, B., Young, N. S. & Brown, K. E. ( 2000; ). Prevalence of the newly described human circovirus, TTV, in United States blood donors. Transfusion 40, 245-251.[CrossRef]
    [Google Scholar]
  11. Hasegawa, M., Kishino, H. & Yano, T. ( 1985; ). Dating of the human–ape splitting by a molecular clock of mitochondrial DNA. Journal of Molecular Evolution 22, 160-174.[CrossRef]
    [Google Scholar]
  12. Hemauer, A., Gigler, A., Searle, K., Beckenlehner, K., Raab, U., Broliden, K., Wolf, H., Enders, G. & Modrow, S. ( 2000; ). Seroprevalence of parvovirus B19 NS1-specific IgG in B19-infected and uninfected individuals and in infected pregnant women. Journal of Medical Virology 60, 48-55.[CrossRef]
    [Google Scholar]
  13. Hijikata, M., Iwata, K., Ohta, Y., Nakao, K., Matsumoto, M., Matsumoto, H., Kanai, K., Baba, K., Samokhvalov, E. I. & Mishiro, S. ( 1999a; ). Genotypes of TT virus (TTV) compared between liver disease patients and healthy individuals using a new PCR system capable of differentiating 1a and 1b types from others. Archives of Virology 144, 2345-2354.[CrossRef]
    [Google Scholar]
  14. Hijikata, M., Takahashi, K. & Mishiro, S. ( 1999b; ). 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]
  15. 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]
  16. Itoh, Y., Takahashi, M., Fukuda, M., Shibayama, T., Ishikawa, T., Tsuda, F., Tanaka, T., Nishizawa, T. & Okamoto, H. ( 2000; ). Visualization of TT virus particles recovered from the sera and feces of infected humans. Biochemical and Biophysical Research Communications 279, 718-724.[CrossRef]
    [Google Scholar]
  17. Kaikkonen, L., Lankinen, H., Harjunpää, I., Hokynar, K., Söderlund-Venermo, M., Oker-Blom, C., Hedman, L. & Hedman, K. ( 1999; ). Acute-phase-specific heptapeptide epitope for diagnosis of parvovirus B19 infection. Journal of Clinical Microbiology 37, 3952-3956.
    [Google Scholar]
  18. Kamahora, T., Hino, S. & Miyata, H. ( 2000; ). Three spliced mRNAs of TT virus transcribed from a plasmid containing the entire genome in COS1 cells. Journal of Virology 74, 9980-9986.[CrossRef]
    [Google Scholar]
  19. Kato, A., Fujino, M., Nakamura, T., Ishihama, A. & Otaki, Y. ( 1995; ). Gene organization of chicken anemia virus. Virology 209, 480-488.[CrossRef]
    [Google Scholar]
  20. Kozak, M. ( 1996; ). Interpreting cDNA sequences: some insights from studies on translation. Mammalian Genome 7, 563-574.[CrossRef]
    [Google Scholar]
  21. Luo, K., Liang, W., He, H., Yang, S., Wang, Y., Xiao, H., Liu, D. & Zhang, L. ( 2000; ). Experimental infection of nonenveloped DNA virus (TTV) in rhesus monkey. Journal of Medical Virology 61, 159-164.[CrossRef]
    [Google Scholar]
  22. Maicas, E., Shago, M. & Friesen, J. D. ( 1990; ). Translation of the Saccharomyces cerevisiae tcm1 gene in the absence of a 5′-untranslated leader. Nucleic Acids Research 18, 5823-5828.[CrossRef]
    [Google Scholar]
  23. Miyata, H., Tsunoda, H., Kazi, A., Yamada, A., Khan, M. A., 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]
  24. Muljono, D. H., Nishizawa, T., Tsuda, F., Takahashi, M. & Okamoto, H. ( 2001; ). Molecular epidemiology of TT virus (TTV) and characterization of two novel TTV genotypes in Indonesia. Archives of Virology 146, 1249-1266.[CrossRef]
    [Google Scholar]
  25. 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]
  26. Niel, C., Saback, F. L. & Lampe, E. ( 2000; ). Coinfection with multiple TT virus strains belonging to different genotypes is a common event in healthy Brazilian adults. Journal of Clinical Microbiology 38, 1926-1930.
    [Google Scholar]
  27. 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]
  28. 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]
  29. Noteborn, M. H. M., Kranenburg, O., Zantema, A., Koch, G., de Boer, G. F. & van der Eb, A. J. ( 1992; ). Transcription of the chicken anemia virus (CAV) genome and synthesis of its 52-kDa protein. Gene 118, 267-271.[CrossRef]
    [Google Scholar]
  30. Okamoto, H. & Mayumi, M. ( 2001; ). TT virus: virological and genomic characteristics and disease associations. Journal of Gastroenterology 36, 519-529.[CrossRef]
    [Google Scholar]
  31. Okamoto, H., Nishizawa, T., Kato, N., Ukita, M., Ikeda, H., Iizuka, H., Miyakawa, Y. & Mayumi, M. ( 1998; ). 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]
  32. Okamoto, H., Takahashi, M., Nishizawa, T., Ukita, M., Fukuda, M., Tsuda, F., Miyakawa, Y. & Mayumi, M. ( 1999a; ). 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]
  33. Okamoto, H., Nishizawa, T., Ukita, M., Takahashi, M., Fukuda, M., Iizuka, H., Miyakawa, Y. & Mayumi, M. ( 1999b; ). 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]
  34. Okamoto, H., Nishizawa, T., Tawara, A., Peng, Y., Takahashi, M., Kishimoto, J., Tanaka, T., Miyakawa, Y. & Mayumi, M. ( 2000a; ). Species-specific TT viruses in humans and nonhuman primates and their phylogenetic relatedness. Virology 277, 368-378.[CrossRef]
    [Google Scholar]
  35. Okamoto, H., Nishizawa, T., Tawara, A., Takahashi, M., Kishimoto, J., Sai, T. & Sugai, Y. ( 2000b; ). TT virus mRNAs detected in the bone marrow cells from an infected individual. Biochemical and Biophysical Research Communications 279, 700-707.[CrossRef]
    [Google Scholar]
  36. Okamoto, H., Nishizawa, T., Takahashi, M., Asabe, S., Tsuda, F. & Yoshikawa, A. ( 2001; ). Heterogeneous distribution of TT virus of distinct genotypes in multiple tissues from infected humans. Virology 288, 358-368.[CrossRef]
    [Google Scholar]
  37. Ott, C., Duret, L., Chemin, I., Trépo, C., Mandrand, B. & Komurian-Pradel, F. ( 2000; ). Use of a TT virus ORF1 recombinant protein to detect anti-TT virus antibodies in human sera. Journal of General Virology 81, 2949-2958.
    [Google Scholar]
  38. Romeo, R., Hegerich, P., Emerson, S. U., Colombo, M., Purcell, R. H. & Bukh, J. ( 2000; ). High prevalence of TT virus (TTV) in naive chimpanzees and in hepatitis C virus-infected humans: frequent mixed infections and identification of new TTV genotypes in chimpanzees. Journal of General Virology 81, 1001-1007.
    [Google Scholar]
  39. 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]
  40. Simmonds, P., Prescott, L. E., Logue, C., Davidson, F., Thomas, A. E. & Ludlam, C. A. ( 1999; ). TT-virus: part of the normal human flora? Journal of Infectious Diseases 180, 1748-1750.
    [Google Scholar]
  41. Söderlund, M., Brown, K. E., Meurman, O. & Hedman, K. ( 1992; ). Prokaryotic expression of a VP1 polypeptide antigen for diagnosis by a human parvovirus B19 antibody enzyme immunoassay. Journal of Clinical Microbiology 30, 305-311.
    [Google Scholar]
  42. Söderlund, M., Brown, C. S., Spaan, W. J. M., Hedman, L. & Hedman, K. ( 1995; ). Epitope type-specific IgG responses to capsid proteins VP1 and VP2 of human parvovirus B19. Journal of Infectious Diseases 172, 1431-1436.[CrossRef]
    [Google Scholar]
  43. Strimmer, K. & von Haesler, A. ( 1997; ). Quartet puzzling: a quartet maximum likelihood method for reconstructing tree topologies. Molecular Biology and Evolution 13, 964-969.
    [Google Scholar]
  44. Suzuki, Y., Taira, H., Tsunoda, T., Mizushima-Sugano, J., Sese, J., Hata, H. and others ( 2001; ). Diverse transcriptional initiation revealed by fine, large-scale mapping of mRNA start sites. EMBO Reports 2, 388–393.[CrossRef]
    [Google Scholar]
  45. Takahashi, K., Iwasa, Y., Hijikata, M. & Mishiro, S. ( 2000; ). Identification of a new human DNA virus (TTV-like mini virus, TLMV) intermediately related to TT virus and chicken anemia virus. Archives of Virology 145, 979-993.[CrossRef]
    [Google Scholar]
  46. Takayama, S., Yamazaki, S., Matsuo, S. & Sugii, S. ( 1999; ). Multiple infection of TT virus (TTV) with different genotypes in Japanese hemophiliacs. Biochemical and Biophysical Research Communications 256, 208-211.[CrossRef]
    [Google Scholar]
  47. Tanaka, Y., Orito, E., Ohno, T., Nakano, T., Hayashi, K., Kato, T., Mukaide, M., Iida, S. & Mizokami, M. ( 2000; ). Identification of a novel 23 kDa protein encoded by putative open reading frame 2 of TT virus (TTV) genotype 1 different from the other genotypes. Archives of Virology 145, 1385-1398.[CrossRef]
    [Google Scholar]
  48. Tawara, A., Akahane, Y., Takahashi, M., Nishizawa, T., Ishikawa, T. & Okamoto, H. ( 2000; ). Transmission of human TT virus of genotype 1a to chimpanzees with fecal supernatant or serum from patients with acute TTV infection. Biochemical and Biophysical Research Communications 278, 470-476.[CrossRef]
    [Google Scholar]
  49. Todd, D., Creelan, J. L., Mackie, D. P., Rixon, F. & McNulty, M. S. ( 1990; ). Purification and biochemical characterization of chicken anaemia agent. Journal of General Virology 71, 819-823.[CrossRef]
    [Google Scholar]
  50. 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]
  51. Tsuda, F., Takahashi, M., Nishizawa, T., Akahane, Y., Konishi, K., Yoshizawa, H. & Okamoto, H. ( 2001; ). IgM-class antibodies to TT virus (TTV) in patients with acute TTV infection. Hepatology Research 19, 1-11.[CrossRef]
    [Google Scholar]
  52. von Poblotzki, A., Gigler, A., Lang, B., Wolf, H. & Modrow, S. ( 1995; ). Antibodies to parvovirus B19 NS-1 protein in infected individuals. Journal of General Virology 76, 519-527.[CrossRef]
    [Google Scholar]
  53. Worobey, M. ( 2000; ). Extensive homologous recombination among widely divergent TT viruses. Journal of Virology 74, 7666-7670.[CrossRef]
    [Google Scholar]
  54. Zehender, G., Manzin, A., De Maddalena, C., Colasante, C., Solforosi, L., Corsi, F., Bianchi-Bosisio, A., Girotto, M., Schirru, I., Russo, U., Galli, M. & Clementi, M. ( 2001; ). Molecular epidemiology of TT virus in Italy and phylogenesis of viral isolates from subjects at different risk for parenteral exposure. Journal of Medical Virology 63, 76-84.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-5-979
Loading
/content/journal/jgv/10.1099/0022-1317-83-5-979
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