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Identification and Molecular Characterization of PERV Gamma1 Long Terminal Repeats

  • Huh, Jae-Won (Division of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Kim, Dae-Soo (Division of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Ha, Hong-Seok (Division of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Ahn, Kung (Division of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Chang, Kyu-Tae (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Byung-Wook (Department of Animal Science, College of Life Sciences, Pusan National University) ;
  • Kim, Heui-Soo (Division of Biological Sciences, College of Natural Sciences, Pusan National University)
  • Received : 2008.08.20
  • Accepted : 2008.11.11
  • Published : 2009.01.31

Abstract

Porcine endogenous retroviruses (PERVs) gamma1 in the pig genome have the potential to act as harmful factors in xenotransplantation (pig-to-human). Long terminal repeats (LTRs) are known to be strong promoter elements that could control the transcription activity of PERV elements and the adjacent functional genes. To investigate the transcribed PERV gamma1 LTR elements in pig tissues, bioinformatic and experimental approaches were conducted. Using RT-PCR amplification and sequencing approaches, 69 different transcribed LTR elements were identified. And 69 LTR elements could be divided into six groups (15 subgroups) by internal variation including tandem repeated sequences, insertion and deletion (INDEL). Remarkably, all internal variations were indentified in U3 region of LTR elements. Taken together, the identification and characterization of various PERV LTR transcripts allow us to extend our knowledge of PERV and its transcriptional study.

Keywords

Acknowledgement

Supported by : Rural Development Administration

References

  1. Akiyoshi, D.E., Denaro, M., Zhu, H., Greenstein, J.L., Banerjee, P.T., and Fishman, J.A. (1998). Identification of a full-length cDNA for an endogenous retrovirus of miniature swine. J. Virol. 72, 4503-4507
  2. Altschul, S.F., Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, W., Miller, W., and Lipman, D.J. (1997). Gapped Blast and PSIBLAST: a new generation of protein database search program. Nucleic Acids Res. 25, 3389-3402 https://doi.org/10.1093/nar/25.17.3389
  3. Czauderna, F., Fischer, N., Boller, K., Kurth, R., and Tonjes, R.R. (2000). Establishment and characterization of molecular clones of porcine endogenous retroviruses replicating on human cells. J. Virol. 74, 4028-4038 https://doi.org/10.1128/JVI.74.9.4028-4038.2000
  4. Denner, J., Specke, V., Thiesen, U., Karlas, A., and Kurth, R. (2003). Genetic alteration of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells. Virology 314, 125-133 https://doi.org/10.1016/S0042-6822(03)00428-8
  5. Dieckhoff, B., Karlas, A., Hofmann, A., Kues, W.A., Petersen, B., Pfeifer, A., Niemann, H., Kurth, R., and Denner, J. (2007). Inhibition of porcine endogenous retroviruses (PERVs). in primary porcine cells by RNA interference using lentiviral vectors. Arch. Virol. 152, 629-634 https://doi.org/10.1007/s00705-006-0868-y
  6. Harrison, I., Takeuchi, Y., Bartosch, B., and Stoye, J.P. (2004). Determinants of high titer in recombinant porcine endogenous retroviruses. J. Virol. 78, 13871-13879 https://doi.org/10.1128/JVI.78.24.13871-13879.2004
  7. Herring, C., Quinn, G., Bower, R., Parsons, N., Logan, N.A., Brawley, A., Elsome, K., Whittam, A., Fernandez-Suarez, X.M., Cunningham, D., et al. (2001). Mapping full-length porcine endogenous retroviruses in a large white pig. J. Virol. 75, 12252-12265 https://doi.org/10.1128/JVI.75.24.12252-12265.2001
  8. Huh, J.W., Hong, K.W., Yi, J.M., Kim, T.H., Takenaka, O., Lee, W.H., and Kim, H.S. (2003). Molecular phylogeny and evolution of the human endogenous retrovirus HERV-W LTR family in hominoid primates. Mol. Cells 15, 122-126
  9. Huh, J.W., Ha, H.S., Kim, Y.J., Lee, J.R., Kim, D.S., Cho, B.W., and Kim, H.S. (2007a). Methylation and promoter activity of long terminal repeats from porcine endogenous retroviruses in the Pig, Sus scrofa. Korean J. Genet. 29, 171-176
  10. Huh, J.W., Cho, B.W., Kim, D.S., Ha, H.S., Yi, J.M., Kim, Y.J., Lee, J.R., Ahn, K., Lee, W.H., and Kim, H.S. (2007b). Long terminal repeats of porcine endogenous retroviruses in Sus scrofa. Arch. Virol. 52, 2271-2276 https://doi.org/10.1007/s00705-007-1049-3
  11. Karlas, A., Kurth, R., and Denner, J. (2004). Inhibition of porcine endogenous retroviruses by RNA interference: increasing the safety of xenotransplantation. Virology 325, 18-23 https://doi.org/10.1016/j.virol.2004.04.022
  12. Klymiuk, N., Muller, M., Brem, G., and Aigner, B. (2006). Phylogeny, recombination and expression of porcine endogenous retrovirus $\gamma$2 nucleotide sequences. J. Gen. Virol. 87, 977-986 https://doi.org/10.1099/vir.0.81552-0
  13. Krach, U., Fischer, N., Czauderna, F., and 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 https://doi.org/10.1128/JVI.75.12.5465-5472.2001
  14. Kumar, S., Tamura, K., Jakobsen, I.B., and Nei, M. (2001). MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17, 1244-1245 https://doi.org/10.1093/bioinformatics/17.12.1244
  15. Le Tissier, P., Stoye, J.P., Takeuchi, Y., Patience, C., and Weiss, R.A. (1997). Two sets of human-tropic pig retrovirus. Nature 389, 681-682 https://doi.org/10.1038/39489
  16. Lee, J.H., Webb, G.C., Allen, R.D., and Moran, C. (2002). Characterizing and mapping porcine endogenous retroviruses in Westran pigs. J. Virol. 76, 5548-5556 https://doi.org/10.1128/JVI.76.11.5548-5556.2002
  17. Ling, J., Pi, W., Bollag, R., Zeng, S., Keskintepe, M., Saliman, H., Krantz, S., Whitney, B., and Tuan, D. (2002). The solitary long terminal repeats of ERV-9 endogenous retrovirus are conserved during primate evolution and possess enhancer activities in embryonic and hematopoietic cells. J. Virol. 76, 2410-2423 https://doi.org/10.1128/jvi.76.5.2410-2423.2002
  18. Mang, R., Maas, J., Chen, X., Goudsmit, J., and van der Kuyl, A.C. (2001). Identification of a novel type C porcine endogenous retrovirus: evidence that copy number of endogenous retroviruses increases during host inbreeding. J. Gen. Virol. 82, 1829-1834 https://doi.org/10.1099/0022-1317-82-8-1829
  19. Martin, U., Kiessl, V., Blusch, H., Haverich, A., von der Helm, K., Herden, T., and Steinhof, G. (1998). Expression of pig endogenous retrovirus by primary porcine endotherial cells and infection of human cells. Lancet 352, 692-694 https://doi.org/10.1016/S0140-6736(98)07144-X
  20. Moalic, Y., Blanchard, Y., Felix, H., and Jestin, A. (2006). Porcine endogenous retrovirus integration sites in the human genome: features in common with those of murine leukemia virus. J. Virol. 80, 10980-10988 https://doi.org/10.1128/JVI.00904-06
  21. Niebert, M., and Tonjes, R.R. (2005). Evolutionary spread and recombination of porcine endogenous retroviruses in the suiformes. J. Virol. 79, 649-654 https://doi.org/10.1128/JVI.79.1.649-654.2005
  22. Niebert, M., Rogel-Gaillard, C., Chardon, P., and Tonjes, R.R. (2002). Characterization of chromosomally assigned replicationcompetent gamma porcine endogenous retroviruses derived from a large white pig and expression in human cells. J. Virol. 76, 2714-2720 https://doi.org/10.1128/JVI.76.6.2714-2720.2002
  23. Patience, C., Takeuchi, Y., and Weiss, R.A. (1997). Infection of human cells by an endogenous retrovirus of pigs. Nat. Med. 3, 282-286 https://doi.org/10.1038/nm0397-282
  24. Patience, C., Switzer, W.M., Takeuchi, Y., Griffiths, D.J., Goward, M.E., Heneine, W., Stoye, J.P., and Weiss, R.A. (2001). Multiple groups of novel retroviral genomes in pigs and related species. J. Virol. 75, 2771-2775 https://doi.org/10.1128/JVI.75.6.2771-2775.2001
  25. Preuss, T., Fischer, N., Boller, K., and Tonjes, R.R. (2006). Isolation and characterization of an infectious replication-competent molecular clone of ecotropic porcine endogenous retrovirus class C. J. Virol. 80, 10258-10261 https://doi.org/10.1128/JVI.01140-06
  26. Quinn, G., and 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 https://doi.org/10.1006/viro.2001.0996
  27. Scheef, G., Fischer, N., Krach, U., and 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 https://doi.org/10.1128/JVI.75.15.6933-6940.2001
  28. Scheef, G., Fischer, N., Flory, E., Schmitt, I., and 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 https://doi.org/10.1128/JVI.76.24.12553-12563.2002
  29. Sellars, M.J., Vuocolo, T., Leeton, L.A., Coman, G.J., Degnan, B.M., and Preston, N.P. (2007). Real-time RT-PCR quantification of Kuruma shrimp transcripts: a comparison of relative and absolute quantification procedures. J. Biotechnol. 129, 391-399 https://doi.org/10.1016/j.jbiotec.2007.01.029
  30. Takefman, D.M., Spear, G.T., Saifuddin, M., and Wilson, C.A. (2002). Human CD59 incorporation into porcine endogenous retrovirus particles: implications for the use of transgenic pigs for xenotransplantation. J. Virol. 76, 1999-2002 https://doi.org/10.1128/JVI.76.4.1999-2002.2002
  31. Takeuchi, Y., Patience, C., Magre, S., Weiss, R.A., Banerjee, P.T., Le Tissier, P., and Stoye, J.P. (1998). Host range and interference studies of three classes of pig endogenous retrovirus. J. Virol. 72, 9986-9991
  32. Tonjes, R.R., and Niebert, M. (2003). Relative age of proviral porcine endogenous retrovirus sequences in Sus scrofa based on the molecular clock hypothesis. J. Virol. 77, 12363-12368 https://doi.org/10.1128/JVI.77.22.12363-12368.2003
  33. Wilson, C.A., Wong, S.W., Muller, J., Davidson, C.E., Rose, T.M., and Burd, P. (1998). Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. J. Virol. 72, 3082-3087
  34. Wilson, C.A., Laeeq, S., Ritzhaupt, A., Colon-Moran, W., and Yoshimura, F.K. (2003). Sequence analysis of porcine endogenous retrovirus long terminal repeats and identification of transcriptional regulatory regions. J. Virol. 77, 142-149 https://doi.org/10.1128/JVI.77.1.142-149.2003
  35. Woods, W.A., Papas, T.S., Hirumi, H., and Chirigos, M.A. (1973). Antigenic and biochemical characterization of the C-type particle of the stable porcine kidney cell line PK-15. J. Virol. 12, 1184-1186

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