Skip to main content
Log in

Structural and quantitative expression analyses of HERV gene family in human tissues

  • Published:
Molecules and Cells

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Blaise, S., de Parseval, N., and Heidmann, T. (2005). Functional characterization of two newly identified human endogenous retrovirus coding envelope genes. Retrovirology 2, 19.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Harris, J.R. (1998). Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance. Bioessays 20, 307–316.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Ruprecht, K., Mayer, J., Sauter, M., Roemer, K., and Mueller-Lantzsch, N. (2008b). Endogenous retroviruses and cancer. Cell. Mol. Life. Sci. 65, 3366–3382.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 antigen-specific immune response in breast cancer patients. Cancer Res. 68, 5869–5877.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heui-Soo Kim.

About this article

Cite this article

Ahn, K., Kim, HS. Structural and quantitative expression analyses of HERV gene family in human tissues. Mol Cells 28, 99–103 (2009). https://doi.org/10.1007/s10059-009-0107-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10059-009-0107-y

Keywords

Navigation