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Structural and Quantitative Expression Analyses of HERV Gene Family in Human Tissues

  • Ahn, Kung (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University)
  • Received : 2009.04.30
  • Accepted : 2009.06.24
  • Published : 2009.08.31

Abstract

Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

Keywords

Acknowledgement

Supported by : Pusan National University

References

  1. Antony, J.M., Zhu, Y., Izad, M., Warren, K.G., Vodjgani, M., Mallet, F., and Power, C. (2007). Comparative expression of human endogenous retrovirus-W genes in multiple sclerosis. AIDS Res. Hum. Retroviruses 23, 1251-1256 https://doi.org/10.1089/aid.2006.0274
  2. Bessis, D., Moles, J.P., Basset-Seguin, N., Tesniere, A., Arpin, C., and Guilhou, J.J. (2004). Differential expression of a human endogenous retrovirus E transmembrane envelope glycoprotein in normal, psoriatic and atopic dermatitis human skin. British J. Dermatol. 151, 737-745 https://doi.org/10.1111/j.1365-2133.2004.06116.x
  3. Blaise, S., de Parseval, N., Benit, L., and Heidmann, T. (2003). Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc. Natl. Acad. Sci . USA 100, 13013-13018 https://doi.org/10.1073/pnas.2132646100
  4. Blaise, S., de Parseval, N., and Heidmann, T. (2005). Functional characterization of two newly identified human endogenous retrovirus coding envelope genes. Retrovirology 2, 19 https://doi.org/10.1186/1742-4690-2-19
  5. Blikstad, V., Benachenhou, F., Sperber, G.O., and Blomberg, J. (2008). Evolution of human endogenous retroviral sequences: a conceptual account. Cell. Mol. Life Sci. 65, 3348-3365 https://doi.org/10.1007/s00018-008-8495-2
  6. Blond, J.L., Lavillette, D., Cheynet, V., Bouton, O., Oriol, G., Chapel- Fernandes, S., Mandrand, B., Mallet, F., and Cosset, F.L. (2000). An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J. Virol. 74, 3321-3329 https://doi.org/10.1128/JVI.74.7.3321-3329.2000
  7. Chang, C., Chen, P.T., Chang, G.D., Huang, C.J., and Chen, H. (2004). Functional characterization of the placental fusogenic membrane protein syncytin. Biol. Reprod. 71, 1956-1962 https://doi.org/10.1095/biolreprod.104.033340
  8. de Parseval, N., Lazar, V., Casella, J.F., Benit, L., and Heidmann, T. (2003). Survey of human genes of retroviral origin: identification and transcriptome of the genes with coding capacity for complete envelope proteins. J. Virol. 77, 10414-10422 https://doi.org/10.1128/JVI.77.19.10414-10422.2003
  9. Dupressoir, A., Marceau, G., Vernochet, C., Benit, L., Kanellopoulos, C., Sapin, V., and Heidmann, T. (2005). Syncytin-A and syncytin- B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. Proc. Natl. Acad. Sci. USA 102, 725-730 https://doi.org/10.1073/pnas.0406509102
  10. Esnault, C., Priet, S., Ribet, D., Vernochet, C., Bruls, T., Lavialle, C., Weissenbach, J., and Heidmann, T. (2008). A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2. Proc. Natl. Acad. Sci. USA 105, 17532-17537 https://doi.org/10.1073/pnas.0807413105
  11. Frank, O., Verbeke, C., Schwarz, N., Mayer, J., Fabarius, A., Hehlmann, R., Leib-Mosch, C., and Seifarth, W. (2008). Variable transcriptional activity of endogenous retroviruses in human breast cancer. J. Virol. 82, 1808-1818 https://doi.org/10.1128/JVI.02115-07
  12. Goedert, J.J., Sauter, M.E., Jacobson, L.P., Vessella, R.L., Hilgartner, M.W., Leitman, S.F., Fraser, M.C., and Mueller-Lantzsch, N.G. (1999). High prevalence of antibodies against HERV-K10 in patients with testicular cancer but not with AIDS. Cancer Epidemiol. Biomarkers Prev. 8, 293-296
  13. Golan, M., Hizi, A., Resau, J.H., Yaal-Hahoshen, N., Reichman, H., Keydar, I., and Tsarfaty, I. (2008). Human endogenous retrovirus (HERV-K) reverse transcriptase as a breast cancer prognostic marker. Neoplasia 10, 521-533 https://doi.org/10.1593/neo.07986
  14. Harris, J.R. (1998). Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance. Bioessays 20, 307-316 https://doi.org/10.1002/(SICI)1521-1878(199804)20:4<307::AID-BIES7>3.0.CO;2-M
  15. Kim, T.H., Jeon, Y.J., Yi, J.M., Kim, D.S., Huh, J.W., Hur, C.G., and Kim, H.S. (2004). The distribution and expression of HERV families in the human genome. Mol. Cells 18, 87-93
  16. Kim, H.S., Yi, J.M., Hirai, H., Huh, J.W., Jeong, M.S., Jang, S.B., Kim, C.G., Saitou, N., Hyun, B.H., and Lee, W.H. (2006). Human Endogenous Retrovirus (HERV)-R family in primates: chromosomal location, gene expression, and evolution. Gene 370, 34-42 https://doi.org/10.1016/j.gene.2005.11.008
  17. Kim, H.S., Kim, D.S., Huh, J.W., Ahn, K., Yi, J.M., Lee, J.R., and Hirai, H. (2008a). Molecular characterization of the HERV-W env gene in humans and primates: expression, FISH, phylogeny, and evolution. Mol. Cells 26, 53-60
  18. Kim, H.S., Ahn, K., and Kim, D.S. (2008b). Quantitative expression of the HERV-W env gene in human tissues. Arch. Virol. 153, 1587-1591 https://doi.org/10.1007/s00705-008-0159-x
  19. Kim, Y.J., Huh, J.W., Kim, D.S., Bae, M.I., Lee, J.R., Ahn, K., Kim, T.O., Song, K.A., and Kim, H.S. (2009). Molecular characterization of the DYX1C1 gene and its application as a cancer biomarker. J. Cancer Res. Clin. Oncol. 135, 265-270 https://doi.org/10.1007/s00432-008-0445-8
  20. Lindeskog, M., Mager, D.L., and Blomberg, J. (1999). Isolation of a human endogenous retroviral HERV-H element with an open env reading frame. Virology 258, 441-450 https://doi.org/10.1006/viro.1999.9750
  21. Mayer, J., Ehlhardt, S., Seifert, M., Sauter, M., Muller-Lantzsch, N., Mehraein, Y., Zang, K.D., and Meese, E. (2004). Human endogenous retrovirus HERV-K (HML-2) proviruses with Rec pro tein coding capacity and transcriptional activity. Virology 322, 190-198 https://doi.org/10.1016/j.virol.2004.01.023
  22. Nellaker, C., Yao, Y., Jones-Brando, L., Mallet, F., Yolken, R.H., and Karlsson, H. (2006). Transactivation of elements in the human endogenous retrovirus W family by viral infection. Retrovirology 3, 44 https://doi.org/10.1186/1742-4690-3-44
  23. Prusty, B.K., zur Hausen, H., Schmidt, R., Kimmel, R., and de Villiers, E.M. (2008). Transcription of HERV-E and HERV-Erelated sequences in malignant and non-malignant human haematopoietic cells. Virology 382, 37-45 https://doi.org/10.1016/j.virol.2008.09.006
  24. Ruprecht, K., Ferreira, H., Flockerzi, A., Wahl, S., Sauter, M., Mayer, J., and Mueller-Lantzsch, N. (2008a). Human endogenous retrovirus family HERV-K (HML-2) RNA transcripts are selectively packaged into retroviral particles produced by the human germ cell tumor line Tera-1 and originate mainly from a provirus on chromosome 22q11.21. J. Virol. 82, 10008-10016 https://doi.org/10.1128/JVI.01016-08
  25. Ruprecht, K., Mayer, J., Sauter, M., Roemer, K., and Mueller- Lantzsch, N. (2008b). Endogenous retroviruses and cancer. Cell. Mol. Life. Sci. 65, 3366-3382 https://doi.org/10.1007/s00018-008-8496-1
  26. Serafino, A., Balestrieri, E., Pierimarchi, P., Matteucci, C., Moroni, G., Oricchio, E., Rasi, G., Mastino, A., Spadafora, C., Garaci, E., et al. (2009). The activation of human endogenous retrovirus K (HERVK) is implicated in melanoma cell malignant transformation. Exp. Cell Res. 315, 849-862 https://doi.org/10.1016/j.yexcr.2008.12.023
  27. Sperber, G.O., Airola, T., Jern, P., and Blomberg, J. (2007). Automated recognition of retroviral sequences in genomic data-- RetroTector. Nucleic Acids Res. 35, 4964-4976 https://doi.org/10.1093/nar/gkm515
  28. Tanaka, S., Ikeda, H., Otsuka, N., Yamamoto, Y., Sugaya, T., and Yoshiki, T. (2003). Tissue specific high level expression of a full length human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats. Transgenic Res. 12, 319-328 https://doi.org/10.1023/A:1023381819572
  29. Tristem, M. (2000). Identification and characterization of the novel human endogenous retrovirus families by phylogenetic screening of the human genome mapping project database. J. Virol. 74, 3715-3730 https://doi.org/10.1128/JVI.74.8.3715-3730.2000
  30. Wang-Johanning, F., Liu, J., Rycaj, K., Huang, M., Tsai, K., Rosen, D.G., Chen, D.T., Lu, D.W., Barnhart, K.F., and Johanning, G.L. (2007). Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer. Int. J. Cancer 120, 81-90 https://doi.org/10.1002/ijc.22256
  31. Wang-Johanning, F., Radvanyi, L., Rycaj, K., Plummer, J.B., Yan, P., Sastry, K.J., Piyathilake, C.J., Hunt, K.K., and Johanning, G.L. (2008). Human endogenous retrovirus K triggers an antigenspecific immune response in breast cancer patients. Cancer Res. 68, 5869-5877 https://doi.org/10.1158/0008-5472.CAN-07-6838
  32. Yi, J.M., and Kim, H.S. (2004). Expression analysis of endo-genous retroviral elements belonging to the HERV-F family from human tissues and cancer cells. Cancer Lett. 211, 89-96 https://doi.org/10.1016/j.canlet.2004.01.026
  33. Yi, J.M., and Kim, H.S. (2007a). Molecular phylogenetic analysis of the human endogenous retrovirus E (HERV-E) family in human tissues and human cancers. Genes Genet. Syst. 82, 89-98 https://doi.org/10.1266/ggs.82.89
  34. Yi, J.M., and Kim, H.S. (2007b). Expression and phylogenetic analyses of human endogenous retrovirus HC2 belonging to the HERV-T family in human tissues and cancer cells. J. Hum. Genet. 52, 285-296 https://doi.org/10.1007/s10038-007-0115-8
  35. Yi, J.M., Kim, T.H., Huh, J.W., Park, K.S., Jang, S.B., Kim, H.M., and Kim, H.S. (2004a). Human endogenous retroviral elements belonging to the HERV-S family from human tissues, cancer cells, and primates: expression, structure, phylogeny and evolution. Gene 342, 283-392 https://doi.org/10.1016/j.gene.2004.08.007
  36. Yi, J.M., Kim, H.M., and Kim, H.S. (2004b). Expression of the human endogenous retrovirus HERV-W family in various human tissues and cancer cells. J. Gen. Virol. 85, 1203-1210 https://doi.org/10.1099/vir.0.79791-0
  37. Yi, J.M., Schuebel, K., and Kim, H.S. (2006a). Molecular genetic analyses of human endogenous retroviral elements belonging to the HERV-P family in primates, human tissues, and cancer cells. Genomics 89, 1-9 https://doi.org/10.1016/j.ygeno.2006.08.010
  38. Yi, J.M., Kim, H.M., and Kim, H.S. (2006b). Human endogenous retrovirus HERV-H family in human tissues and cancer cells: expression, identification, and phylogeny. Cancer Lett. 231, 228-239 https://doi.org/10.1016/j.canlet.2005.02.001
  39. Yi, J.M., Schuebel, K., and Kim, H.S. (2007). Molecular genetic analyses of human endogenous retroviral elements belonging to the HERV-P family in primates, human tissues, and cancer cells. Genomics 89, 1-9 https://doi.org/10.1016/j.ygeno.2006.08.010

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