Characterization of germline porcine endogenous retroviruses from Large White pig Free

Abstract

Porcine endogenous retroviruses (PERV) are of concern when the microbiological safety aspects of xenotransplantation are considered. Four unique isolates of PERV B have been identified previously from a lambda library constructed from genomic DNA from a Large White pig. This study shows that none of these isolates are replication competent when transfected into permissive human or pig cells , and the removal of flanking genomic sequences does not confer a human tropic replication competent (HTRC) phenotype on these PERV proviruses. Analysis of the envelope sequences revealed that PERV B demonstrated high similarity to the envelope sequences derived from replication-competent PERV, indicating that lack of replication competence does not appear to be attributable to this region of the provirus. These data complement recent findings that HTRC PERV are recombinants between the PERV A and PERV C subgroups, and that these recombinants are not present in the germline of miniature swine. Together, these results indicate that these individual PERV B proviruses are unlikely to give rise to HTRC PERV.

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2004-08-01
2024-03-29
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References

  1. Ausubel F. M., Brent R., Kingston R. E., Moore D. D., Seidman J. G., Smith J. A., Struhl K. 1997 Current Protocols in Molecular Biology New York: Wiley;
    [Google Scholar]
  2. Bartosch B., Weiss R. A., Takeuchi Y. 2002; PCR-based cloning and immunocytological titration of infectious porcine endogenous retrovirus subgroup A and B. J Gen Virol 83:2231–2240
    [Google Scholar]
  3. Cosset F. L., Takeuchi Y., Battini J. L., Weiss R. A., Collins M. K. 1995; High-titer packaging cells producing recombinant retroviruses resistant to human serum. J Virol 69:7430–7436
    [Google Scholar]
  4. Czauderna F., Fischer N., Boller K., Kurth R., Tonjes R. R. 2000; Establishment and characterization of molecular clones of porcine endogenous retroviruses replicating on human cells. J Virol 74:4028–4038 [CrossRef]
    [Google Scholar]
  5. Deng Y. M., Tuch B. E., Rawlinson W. D. 2000; Transmission of porcine endogenous retroviruses in severe combined immunodeficient mice xenotransplanted with fetal porcine pancreatic cells. Transplantation 70:1010–1016 [CrossRef]
    [Google Scholar]
  6. Herring C., Quinn G., Bower R. 10 other authors 2001; Mapping full-length porcine endogenous retroviruses in a large white pig. J Virol 75:12252–12265 [CrossRef]
    [Google Scholar]
  7. Krach U., Fischer N., Czauderna F., Tonjes R. R. 2001; Comparison of replication-competent molecular clones of porcine endogenous retrovirus class A and class B derived from pig and human cells. J Virol 75:5465–5472 [CrossRef]
    [Google Scholar]
  8. 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 [CrossRef]
    [Google Scholar]
  9. Niebert M., Rogel-Gaillard C., Chardon P., Tonjes R. R. 2002; Characterization of chromosomally assigned replication-competent gamma porcine endogenous retroviruses derived from a large white pig and expression in human cells. J Virol 76:2714–2720 [CrossRef]
    [Google Scholar]
  10. Oldmixon B. A., Wood J. C., Ericsson T. A., Wilson C. A., White-Scharf M. E., Andersson G., Greenstein J. L., Schuurman H. J., Patience C. 2002; Porcine endogenous retrovirus transmission characteristics of an inbred herd of miniature swine. J Virol 76:3045–3048 [CrossRef]
    [Google Scholar]
  11. Patience C., Takeuchi Y., Weiss R. A. 1997; Infection of human cells by an endogenous retrovirus of pigs. Nat Med 3:282–286 [CrossRef]
    [Google Scholar]
  12. Quinn G., Langford G. 2001; The porcine endogenous retrovirus long terminal repeat contains a single nucleotide polymorphism that confers distinct differences in estrogen receptor binding affinity between PERV A and PERV B/C subtypes. Virology 286:83–90 [CrossRef]
    [Google Scholar]
  13. Quinn G., Ochiya T., Terada M., Yoshida T. 2000; Mouse flt-1 promoter directs endothelial-specific expression in the embyroid body model of embryogenesis. Biochem Biophys Res Commun 276:1089–1099 [CrossRef]
    [Google Scholar]
  14. Scheef G., Fischer N., Krach U., Tonjes R. R. 2001; The number of a U3 repeat box acting as an enhancer in long terminal repeats of polytropic replication-competent porcine endogenous retroviruses dynamically fluctuates during serial virus passages in human cells. J Virol 75:6933–6940 [CrossRef]
    [Google Scholar]
  15. Scheef G., Fischer N., Flory E., Schmitt I., Tonjes R. R. 2002; Transcriptional regulation of porcine endogenous retroviruses released from porcine and infected human cells by heterotrimeric protein complex NF-Y and impact of immunosuppressive drugs. J Virol 76:12553–12563 [CrossRef]
    [Google Scholar]
  16. Scobie L., Taylor S., Wood J. C., Suling K. M., Quinn G., Meikle S., Patience C., Onions D. 2004; Absence of replication-competent human-tropic porcine endogenous retroviruses in the germ line DNA of inbred miniature swine. J Virol 78:2502–2509 [CrossRef]
    [Google Scholar]
  17. Specke V., Rubant S., Denner J. 2001a; Productive infection of human primary cells and cell lines with porcine endogenous retroviruses. Virology 285:177–180 [CrossRef]
    [Google Scholar]
  18. Specke V., Tacke S. J., Boller K., Schwendemann J., Denner J. 2001b; Porcine endogenous retroviruses: in vitro host range and attempts to establish small animal models. J Gen Virol 82:837–844
    [Google Scholar]
  19. Stoye J. P., Le Tissier P., Takeuchi Y., Patience C., Weiss R. A. 1998; Endogenous retroviruses: a potential problem for xenotransplantation?. Ann N Y Acad Sci 862:67–74 [CrossRef]
    [Google Scholar]
  20. Takeuchi Y., Weiss R. A. 2000; Xenotransplantation: reappraising the risk of retroviral zoonosis. Curr Opin Immunol 12:504–507 [CrossRef]
    [Google Scholar]
  21. Takeuchi Y., Patience C., Magre S., Weiss R. A., Banerjee P. T., Le Tissier P., Stoye J. P. 1998; Host range and interference studies of three classes of pig endogenous retrovirus. J Virol 72:9986–9991
    [Google Scholar]
  22. van der Laan L. J., Lockey C., Griffeth B. C. 8 other authors 2000; Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice. Nature 407:90–94 [CrossRef]
    [Google Scholar]
  23. 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
    [Google Scholar]
  24. Wilson C. A., Wong S., VanBrocklin M., Federspiel M. J. 2000; Extended analysis of the in vitro tropism of porcine endogenous retrovirus. J Virol 74:49–56 [CrossRef]
    [Google Scholar]
  25. Wilson C. A., Laeeq S., Ritzhaupt A., Colon-Moran W., Yoshimura F. K. 2003; Sequence analysis of porcine endogenous retrovirus long terminal repeats and identification of transcriptional regulatory regions. J Virol 77:142–149 [CrossRef]
    [Google Scholar]
  26. Wood J., Quinn G., Suling K. 11 other authors 2004; Identification of exogenous forms of human-tropic porcine endogenous retrovirus in miniature swine. J Virol 78:2494–2501 [CrossRef]
    [Google Scholar]
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