1887

Abstract

Recently, we immunized different mammalian species (goats, mice, rats, rabbits, guinea pigs and hamsters) with the recombinant ectodomain of the transmembrane envelope (TM) protein p15E of porcine endogenous retrovirus (PERV). In all cases, neutralizing immune sera were induced, which recognized epitopes in the fusion peptide proximal region and the membrane proximal external region of p15E. In order to analyse whether pigs are also able to produce such antibodies, and whether such antibodies can be used to study the involvement of the TM protein in placental development (as was shown for endogenous retroviruses of other species), German landrace pigs were immunized with PERV p15E. No binding and neutralizing antibodies were produced as shown in three Western blot analyses and in a neutralization assay, indicating that pigs are tolerant to their endogenous retroviruses, at least for the ectodomain of the TM protein.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.064857-0
2014-08-01
2024-03-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/8/1827.html?itemId=/content/journal/jgv/10.1099/vir.0.064857-0&mimeType=html&fmt=ahah

References

  1. Bittmann I., Mihica D., Plesker R., Denner J. 2012; Expression of porcine endogenous retroviruses (PERV) in different organs of a pig. Virology 433:329–336 [View Article][PubMed]
    [Google Scholar]
  2. Büscher K., Trefzer U., Hofmann M., Sterry W., Kurth R., Denner J. 2005; Expression of human endogenous retrovirus K in melanomas and melanoma cell lines. Cancer Res 65:4172–4180 [View Article][PubMed]
    [Google Scholar]
  3. Büscher K., Hahn S., Hofmann M., Trefzer U., Ozel M., Sterry W., Löwer J., Löwer R., Kurth R., Denner J. 2006; Expression of the human endogenous retrovirus-K transmembrane envelope, Rec and Np9 proteins in melanomas and melanoma cell lines. Melanoma Res 16:223–234 [View Article][PubMed]
    [Google Scholar]
  4. Denner J. 2008; Recombinant porcine endogenous retroviruses (PERV-A/C): a new risk for xenotransplantation?. Arch Virol 153:1421–1426 [View Article][PubMed]
    [Google Scholar]
  5. Denner J. 2010; Endogenous retroviruses. In Retroviruses: Molecular Biology, Genomics and Pathogenesis pp. 35–69 Edited by Kurth R., Bannert N. Hethersett, Norwich: Caister Academic Press;
    [Google Scholar]
  6. Denner J., Tönjes R. R. 2012; Infection barriers to successful xenotransplantation focusing on porcine endogenous retroviruses. Clin Microbiol Rev 25:318–343 [View Article][PubMed]
    [Google Scholar]
  7. Denner J., Specke V., Thiesen U., Karlas A., Kurth R. 2003; Genetic alterations of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells. Virology 314:125–133 [View Article][PubMed]
    [Google Scholar]
  8. Denner J., Mihica D., Kaulitz D., Schmidt C. M. 2012; Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs). Virol J 9:260 [View Article][PubMed]
    [Google Scholar]
  9. Fiebig U., Stephan O., Kurth R., Denner J. 2003; Neutralizing antibodies against conserved domains of p15E of porcine endogenous retroviruses: basis for a vaccine for xenotransplantation?. Virology 307:406–413 [View Article][PubMed]
    [Google Scholar]
  10. Hanna M. G. Jr, Ihle J. N., Batzing B. L., Tennant T. W., Schenley C. K. 1975; Assessment of reactivities of natural antibodies to endogenous RNA tumor virus envelope antigens and virus-induced cell surface antigens. Cancer Res 35:164–171[PubMed]
    [Google Scholar]
  11. Huebner R. J., Sarma P., Kelloff G., Gilden R., Meier H., Myers D., Peters R. 1971; Immunological tolerance to RNA tumor virus genome expressions: significance of tolerance and prenatal expressions in embryogenesis and tumerogenesis. Ann N Y Acad Sci 181:246–271 [View Article]
    [Google Scholar]
  12. Ihle J. N., Hanna M. G. Jr 1977; Natural immunity to endogenous oncornaviruses in mice. Contemp Top Immunobiol 6:169–194 [View Article][PubMed]
    [Google Scholar]
  13. Ihle J. N., Yurconic M. Jr, Hanna M. G. Jr 1973; Autogenous immunity to endogenous RNA tumor virus. Radioimmune precipitation assay of mouse serum antibody levels. J Exp Med 138:194–208 [View Article][PubMed]
    [Google Scholar]
  14. Kämmerer U., Germeyer A., Stengel S., Kapp M., Denner J. 2011; Human endogenous retrovirus K (HERV-K) is expressed in villous and extravillous cytotrophoblast cells of the human placenta. J Reprod Immunol 91:1–8[PubMed]
    [Google Scholar]
  15. Karlas A., Irgang M., Votteler J., Specke V., Ozel M., Kurth R., Denner J. 2010; Characterisation of a human cell-adapted porcine endogenous retrovirus PERV-A/C. Ann Transplant 15:45–54[PubMed]
    [Google Scholar]
  16. Kaulitz D., Fiebig U., Eschricht M., Wurzbacher C., Kurth R., Denner J. 2011; Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs). Virology 411:78–86 [View Article][PubMed]
    [Google Scholar]
  17. Koraka P., Burghoorn-Maas C. P., Falconar A., Setiati T. E., Djamiatun K., Groen J., Osterhaus A. D. 2003; Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections. J Clin Microbiol 41:4154–4159 [View Article][PubMed]
    [Google Scholar]
  18. Langhammer S., Fiebig U., Kurth R., Denner J. 2005; Neutralising antibodies against the transmembrane protein of feline leukaemia virus (FeLV). Vaccine 23:3341–3348 [View Article][PubMed]
    [Google Scholar]
  19. Langhammer S., Hübner J., Kurth R., Denner J. 2006; Antibodies neutralizing feline leukaemia virus (FeLV) in cats immunized with the transmembrane envelope protein p15E. Immunology 117:229–237 [View Article][PubMed]
    [Google Scholar]
  20. Langhammer S., Fiebig U., Kurth R., Denner J. 2011a; Increased neutralizing antibody response after simultaneous immunization with leucogen and the feline leukemia virus transmembrane protein. Intervirology 54:78–86 [View Article][PubMed]
    [Google Scholar]
  21. Langhammer S., Hübner J., Jarrett O., Kurth R., Denner J. 2011b; Immunization with the transmembrane protein of a retrovirus, feline leukemia virus: absence of antigenemia following challenge. Antiviral Res 89:119–123 [View Article][PubMed]
    [Google Scholar]
  22. Lavialle C., Cornelis G., Dupressoir A., Esnault C., Heidmann O., Vernochet C., Heidmann T. 2013; Paleovirology of ‘syncytins’, retroviral env genes exapted for a role in placentation. Philos Trans R Soc Lond B Biol Sci 368:20120507 [View Article][PubMed]
    [Google Scholar]
  23. Le Tissier P., Stoye J. P., Takeuchi Y., Patience C., Weiss R. A. 1997; Two sets of human-tropic pig retrovirus. Nature 389:681–682 [View Article][PubMed]
    [Google Scholar]
  24. Löwer R., Löwer J., Kurth R. 1996; The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc Natl Acad Sci U S A 93:5177–5184 [View Article][PubMed]
    [Google Scholar]
  25. Mangeney M., Renard M., Schlecht-Louf G., Bouallaga I., Heidmann O., Letzelter C., Richaud A., Ducos B., Heidmann T. 2007; Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins. Proc Natl Acad Sci U S A 104:20534–20539 [View Article][PubMed]
    [Google Scholar]
  26. Miyazawa M., Fujisawa R. 1994; Physiology and pathology of host immune responses to exogenous and endogenous murine retroviruses – from gene fragments to epitopes. Tohoku J Exp Med 173:91–103 [View Article][PubMed]
    [Google Scholar]
  27. Morozov V. A., Dao Thi V. L., Denner J. 2013; The transmembrane protein of the human endogenous retrovirus-K (HERV-K) modulates cytokine release and gene expression. PLoS ONE 8:e70399 [View Article][PubMed]
    [Google Scholar]
  28. Muster T., Waltenberger A., Grassauer A., Hirschl S., Caucig P., Romirer I., Födinger D., Seppele H., Schanab O.other authors 2003; An endogenous retrovirus derived from human melanoma cells. Cancer Res 63:8735–8741[PubMed]
    [Google Scholar]
  29. Oldstone M. B., Aoki T., Dixon F. J. 1972; The antibody response of mice to murine leukemia virusin spontaneous infection: absence of classical immunologic tolerance. Proc Natl Acad Sci U S A 69:134–138 [View Article][PubMed]
    [Google Scholar]
  30. Oldstone M. B., Del Villano B. C., Dixon F. J. 1976; Autologous immune responses to the major oncornavirus polypeptides in unmanipulated AKR/J mice. J Virol 18:176–181[PubMed]
    [Google Scholar]
  31. Patience C., Takeuchi Y., Weiss R. A. 1997; Infection of human cells by an endogenous retrovirus of pigs. Nat Med 3:282–286 [View Article][PubMed]
    [Google Scholar]
  32. Specke V., Rubant S., Denner J. 2001; Productive infection of human primary cells and cell lines with porcine endogenous retroviruses. Virology 285:177–180 [View Article][PubMed]
    [Google Scholar]
  33. Tacke S. J., Specke V., Denner J. 2003; Differences in release and determination of subtype of porcine endogenous retroviruses produced by stimulated normal pig blood cells. Intervirology 46:17–24 [View Article][PubMed]
    [Google Scholar]
  34. Waechter A., Eschricht M., Denner J. 2013; Neutralization of porcine endogenous retrovirus by antibodies against the membrane-proximal external region of the transmembrane envelope protein. J Gen Virol 94:643–651 [View Article][PubMed]
    [Google Scholar]
  35. Wilson C. A. 2008; Endogenous retroviruses. Cell Mol Life Sci 65:3399–3412 [View Article][PubMed]
    [Google Scholar]
  36. Wilson C. A., Wong S., Muller J., Davidson C. E., Rose T. M., Burd P. 1998; Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. J Virol 72:3082–3087[PubMed]
    [Google Scholar]
  37. Zwick M. B., Labrijn A. F., Wang M., Spenlehauer C., Saphire E. O., Binley J. M., Moore J. P., Stiegler G., Katinger H.other authors 2001; Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol 75:10892–10905 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.064857-0
Loading
/content/journal/jgv/10.1099/vir.0.064857-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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