1887

Abstract

Torque teno viruses (TTVs) circulate widely among humans, causing persistent viraemia in healthy individuals. Numerous TTV isolates with high genetic variability have been identified and segregated into 29 species of five major phylogenetic groups. To date, the diversity of TTV sequences, challenges in protein expression and the subsequent lack of serological assays have hampered TTV seroprevalence studies. Moreover, the antigenic relationships of different TTVs and their specific seroprevalences in humans remain unknown. For five TTV strains – belonging to different species of four genogroups – we developed, using recombinant glutathione -transferase (GST)-fused TTV ORF2 proteins, glutathione–GST capture enzyme immunoassays (EIAs) detecting antibodies towards conformational epitopes. We then analysed serum samples from 178 healthy adults and 108 children; IgG reactivities were observed either towards a single strain or towards multiple strains, which pointed to antigenic distinction of TTV species. The overall seroprevalence for the five TTVs peaked at 43 % (18 of 42) in children 2–4 years of age, subsequently declined, and again reached 42 % (74 of 178) among adults. species-specific IgG predominated in children, whereas that for predominated in adults. During a 3 year follow-up of the same children, both species-specific seroconversions and seroreversions occurred. This is the first EIA-based study of different TTVs, providing a new approach for seroepidemiology and diagnosis of TTV infections. Our data suggest that different TTVs in humans may differ in antiviral antibody profiles, infection patterns and epidemiology.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.046862-0
2013-02-01
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/2/409.html?itemId=/content/journal/jgv/10.1099/vir.0.046862-0&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.. & other authors ( 1999;). TT virus infection is widespread in the general populations from different geographic regions. . J Clin Microbiol 37:, 2703–2705.[PubMed]
    [Google Scholar]
  2. Biagini P.. ( 2009;). Classification of TTV and related viruses (anelloviruses). . Curr Top Microbiol Immunol 331:, 21–33. [CrossRef][PubMed]
    [Google Scholar]
  3. Biagini P., Gallian P., Cantaloube J. F., Attoui H., de Micco P., de Lamballerie X.. ( 2006;). Distribution and genetic analysis of TTV and TTMV major phylogenetic groups in French blood donors. . J Med Virol 78:, 298–304. [CrossRef][PubMed]
    [Google Scholar]
  4. Chen T., Mattila P. S., Jartti T., Ruuskanen O., Söderlund-Venermo M., Hedman K.. ( 2011a;). Seroepidemiology of the newly found trichodysplasia spinulosa-associated polyomavirus. . J Infect Dis 204:, 1523–1526. [CrossRef][PubMed]
    [Google Scholar]
  5. Chen T., Hedman L., Mattila P. S., Jartti T., Ruuskanen O., Söderlund-Venermo M., Hedman K.. ( 2011b;). Serological evidence of Merkel cell polyomavirus primary infections in childhood. . J Clin Virol 50:, 125–129. [CrossRef][PubMed]
    [Google Scholar]
  6. de Villiers E. M., Schmidt R., Delius H., zur Hausen H.. ( 2002;). Heterogeneity of TT virus related sequences isolated from human tumour biopsy specimens. . J Mol Med (Berl) 80:, 44–50. [CrossRef][PubMed]
    [Google Scholar]
  7. Devalle S., Niel C.. ( 2004;). Distribution of TT virus genomic groups 1–5 in Brazilian blood donors, HBV carriers, and HIV-1-infected patients. . J Med Virol 72:, 166–173. [CrossRef][PubMed]
    [Google Scholar]
  8. Diniz-Mendes L., Devalle S., Niel C.. ( 2004;). Genomic characterization of a Brazilian TT virus isolate closely related to SEN virus-F. . Mem Inst Oswaldo Cruz 99:, 301–306. [CrossRef][PubMed]
    [Google Scholar]
  9. Erker J. C., Leary T. P., Desai S. M., Chalmers M. L., Mushahwar I. K.. ( 1999;). Analyses of TT virus full-length genomic sequences. . J Gen Virol 80:, 1743–1750.[PubMed]
    [Google Scholar]
  10. Hammarén-Malmi S., Saxén H., Tarkkanen J., Mattila P. S.. ( 2005;). Adenoidectomy does not significantly reduce the incidence of otitis media in conjunction with the insertion of tympanostomy tubes in children who are younger than 4 years: a randomized trial. . Pediatrics 116:, 185–189. [CrossRef][PubMed]
    [Google Scholar]
  11. 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][PubMed]
    [Google Scholar]
  12. Huang L. Y., Jonassen T. O., Hungnes O., Grinde B.. ( 2001;). High prevalence of TT virus-related DNA (90 %) and diverse viral genotypes in Norwegian blood donors. . J Med Virol 64:, 381–386. [CrossRef][PubMed]
    [Google Scholar]
  13. Huang Y. W., Harrall K. K., Dryman B. A., Opriessnig T., Vaughn E. M., Roof M. B., Meng X. J.. ( 2012;). Serological profile of torque teno sus virus species 1 (TTSuV1) in pigs and antigenic relationships between two TTSuV1 genotypes (1a and 1b), between two species (TTSuV1 and -2), and between porcine and human anelloviruses. . J Virol 86:, 10628–10639. [CrossRef][PubMed]
    [Google Scholar]
  14. Jelcic I., Hotz-Wagenblatt A., Hunziker A., Zur Hausen H., de Villiers E. M.. ( 2004;). Isolation of multiple TT virus genotypes from spleen biopsy tissue from a Hodgkin’s disease patient: genome reorganization and diversity in the hypervariable region. . J Virol 78:, 7498–7507. [CrossRef][PubMed]
    [Google Scholar]
  15. Kakkola L., Hedman K., Vanrobaeys H., Hedman L., Söderlund-Venermo M.. ( 2002;). Cloning and sequencing of TT virus genotype 6 and expression of antigenic open reading frame 2 proteins. . J Gen Virol 83:, 979–990.[PubMed]
    [Google Scholar]
  16. Kakkola L., Kaipio N., Hokynar K., Puolakkainen P., Mattila P. S., Kokkola A., Partio E. K., Eis-Hübinger A. M., Söderlund-Venermo M., Hedman K.. ( 2004;). Genoprevalence in human tissues of TT-virus genotype 6. . Arch Virol 149:, 1095–1106. [CrossRef][PubMed]
    [Google Scholar]
  17. Kakkola L., Bondén H., Hedman L., Kivi N., Moisala S., Julin J., Ylä-Liedenpohja J., Miettinen S., Kantola K.. & other authors ( 2008;). Expression of all six human Torque teno virus (TTV) proteins in bacteria and in insect cells, and analysis of their IgG responses. . Virology 382:, 182–189. [CrossRef][PubMed]
    [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. . J Virol 74:, 9980–9986. [CrossRef][PubMed]
    [Google Scholar]
  19. Kazi A., Miyata H., Kurokawa K., Khan M. A., Kamahora T., Katamine S., Hino S.. ( 2000;). High frequency of postnatal transmission of TT virus in infancy. . Arch Virol 145:, 535–540. [CrossRef][PubMed]
    [Google Scholar]
  20. Biagini P., Bendinelli M., Hino S., Kakkola L., Mankertz A., Niel C., Okamoto H., Raidal S., Teo C.G., Todd D.. ( 2011;). Anelloviridae. . In Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses, pp. 331–341. Edited by King A. M. Q., Adams M. J., Carstens E. B., Lefkowitz E. J... London, San Diego:: Elsevier Academic Press;.
    [Google Scholar]
  21. Leppik L., Gunst K., Lehtinen M., Dillner J., Streker K., de Villiers E. M.. ( 2007;). In vivo and in vitro intragenomic rearrangement of TT viruses. . J Virol 81:, 9346–9356. [CrossRef][PubMed]
    [Google Scholar]
  22. Lin H. H., Kao J. H., Lee P. I., Chen D. S.. ( 2002;). Early acquisition of TT virus in infants: possible minor role of maternal transmission. . J Med Virol 66:, 285–290. [CrossRef][PubMed]
    [Google Scholar]
  23. Maggi F., Fornai C., Vatteroni M. L., Siciliano G., Menichetti F., Tascini C., Specter S., Pistello M., Bendinelli M.. ( 2001;). Low prevalence of TT virus in the cerebrospinal fluid of viremic patients with central nervous system disorders. . J Med Virol 65:, 418–422. [CrossRef][PubMed]
    [Google Scholar]
  24. Maggi F., Andreoli E., Lanini L., Fornai C., Vatteroni M., Pistello M., Presciuttini S., Bendinelli M.. ( 2005;). Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried. . J Clin Microbiol 43:, 4807–4810. [CrossRef][PubMed]
    [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., Dexai S. M.. ( 1999;). Molecular and biophysical characterization of TT virus: evidence for a new virus family infecting humans. . Proc Natl Acad Sci U S A 96:, 3177–3182. [CrossRef][PubMed]
    [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. . J Clin Microbiol 38:, 1926–1930.[PubMed]
    [Google Scholar]
  27. Niel C., Diniz-Mendes L., Devalle S.. ( 2005;). Rolling-circle amplification of Torque teno virus (TTV) complete genomes from human and swine sera and identification of a novel swine TTV genogroup. . J Gen Virol 86:, 1343–1347. [CrossRef][PubMed]
    [Google Scholar]
  28. Ninomiya M., Takahashi M., Nishizawa T., Shimosegawa T., Okamoto H.. ( 2008;). Development of PCR assays with nested primers specific for differential detection of three human anelloviruses and early acquisition of dual or triple infection during infancy. . J Clin Microbiol 46:, 507–514. [CrossRef][PubMed]
    [Google Scholar]
  29. 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. . Biochem Biophys Res Commun 241:, 92–97. [CrossRef][PubMed]
    [Google Scholar]
  30. Okamoto H.. ( 2009;). History of discoveries and pathogenicity of TT viruses. . Curr Top Microbiol Immunol 331:, 1–20. [CrossRef][PubMed]
    [Google Scholar]
  31. 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][PubMed]
    [Google Scholar]
  32. 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. . J Gen Virol 81:, 2949–2958.[PubMed]
    [Google Scholar]
  33. Peng Y. H., Nishizawa T., Takahashi M., Ishikawa T., Yoshikawa A., Okamoto H.. ( 2002;). Analysis of the entire genomes of thirteen TT virus variants classifiable into the fourth and fifth genetic groups, isolated from viremic infants. . Arch Virol 147:, 21–41. [CrossRef][PubMed]
    [Google Scholar]
  34. Qiu J., Kakkola L., Cheng F., Ye C., Söderlund-Venermo M., Hedman K., Pintel D. J.. ( 2005;). Human circovirus TT virus genotype 6 expresses six proteins following transfection of a full-length clone. . J Virol 79:, 6505–6510. [CrossRef][PubMed]
    [Google Scholar]
  35. Sehr P., Zumbach K., Pawlita M.. ( 2001;). A generic capture ELISA for recombinant proteins fused to glutathione S-transferase: validation for HPV serology. . J Immunol Methods 253:, 153–162. [CrossRef][PubMed]
    [Google Scholar]
  36. Sehr P., Müller M., Höpfl R., Widschwendter A., Pawlita M.. ( 2002;). HPV antibody detection by ELISA with capsid protein L1 fused to glutathione S-transferase. . J Virol Methods 106:, 61–70. [CrossRef][PubMed]
    [Google Scholar]
  37. Simmonds P., Prescott L. E., Logue C., Davidson F., Thomas A. E., Ludlam C. A.. ( 1999;). TT virus – part of the normal human flora?. J Infect Dis 180:, 1748–1749. [CrossRef][PubMed]
    [Google Scholar]
  38. Toyoda H., Naruse M., Yokozaki S., Morita K., Nakano I., Itakura A., Okamura M., Fukuda Y., Hayakawa T.. ( 1999;). Prevalence of infection with TT virus (TTV), a novel DNA virus, in healthy Japanese subjects, newborn infants, cord blood and breast milk. . J Infect 38:, 198–199. [CrossRef][PubMed]
    [Google Scholar]
  39. 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. . J Virol Methods 77:, 199–206. [CrossRef][PubMed]
    [Google Scholar]
  40. 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. . Hepatol Res 19:, 1–11. [CrossRef][PubMed]
    [Google Scholar]
  41. Zheng H., Ye L., Fang X., Li B., Wang Y., Xiang X., Kong L., Wang W., Zeng Y.. & other authors ( 2007;). Torque teno virus (SANBAN isolate) ORF2 protein suppresses NF-κB pathways via interaction with IκB kinases. . J Virol 81:, 11917–11924. [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.046862-0
Loading
/content/journal/jgv/10.1099/vir.0.046862-0
Loading

Data & Media loading...

Supplementary material 

PDF

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