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Human endogenous retroviruses: Their possible role in the molecular etiology of the schizophrenia

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DOI: 10.4236/ojgen.2012.21009    5,509 Downloads   10,079 Views   Citations

ABSTRACT

Human endogenous retroviruses (HERVs) represent footprints of previous retroviral infections. They are integrated within the human germ line and constitute approximately 8% of our genome. They have the potential to harm, given their capacity to alter the cellular metabolism, and could be involved in various pathological processes. This revision intends to highlight the importance of HERVs in health and disease, and the increasing interest of the scientific community in their biology. In this overview, we will present a brief summary of the structure and physiological function of HERVs and an analysis of their role in schizophrenia, a paradigm of mental illness, particularly stressing the importance of HERV research to explore the more basic mechanisms disrupted in this psychiatric condition.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Alelú-Paz, R. and Iturrieta-Zuazo, I. (2012) Human endogenous retroviruses: Their possible role in the molecular etiology of the schizophrenia. Open Journal of Genetics, 2, 70-76. doi: 10.4236/ojgen.2012.21009.

References

[1] Baltimore, D. (1970). Rna-dependent DNA polymerase in virions of RNA tumour viruses. Nature, 226, 1209-1211. doi:10.1038/2261209a0
[2] Temin, H.M. and Mizutani, S. (1970) Rna-dependent DNA polymerase in virions of rous sarcoma virus. Nature, 226, 1211-123. doi:10.1038/2261211a0
[3] Martin, M.A., Bryan, T., Rasheed, S. and Kahn, A.S. (1981) Identification and cloning of endogenous retroviral sequences present in human DNA. Proceedings of the National Academy of Sciences of the United States of America, 78, 4892-4896. doi:10.1073/pnas.78.8.4892
[4] Bonner, T.I, O’Connell, C. and Cohen, M. (1982) Cloned endogenous retroviral sequences from human DNA. Proceedings of the National Academy of Sciences of the United States of America, 79, 4709-4713. doi:10.1073/pnas.79.15.4709
[5] Lander, E.S., Linton, L.M., Birren, B., et al. International Human Genome Sequencing Consortium). (2001) Initial sequencing and analysis of the human genome. Nature, 409, 860-921. doi:10.1038/35057062
[6] Venter, J.C., Adams, M.D., Myers, E.W., et al. (2001) The sequence of the human genome. Science, 291, 1304-1351. doi:10.1126/science.1058040
[7] Lower, R., Lower, J. and Kurth, R. (1996) The viruses in all of us: Characteristics and biological significance of human endogenous retrovirus sequences. Proceedings of the National Academy of Sciences of the United States of America, 93, 5177-5184. doi:10.1073/pnas.93.11.5177
[8] Baumann, J.G. (2006) Intracellular restriction factors in mammalian cells—An ancient defense system finds a modern foe. Current HIV Research, 4, 141-168. doi:10.2174/157016206776055093
[9] Towers, G.J. (2005) Control of viral infectivity by tripartite motif proteins. Human Gene Therapy, 16, 1125-1132. doi:10.1089/hum.2005.16.1125
[10] Cullen, B.R. (2006) Role and mechanism of action of the apobec3 family of antiretroviral resistance factors. Journal of Virology, 80, 1067-1076. doi:10.1128/JVI.80.3.1067-1076.2006
[11] Blikstad, V., Benachenhou, F., Sperber, G.O. and Blomberg, J. (2008) Evolution of human endogenous retroviral sequences: A conceptual account. Cellular and Molecular Life Sciences, 65, 3348-3365. doi:10.1007/s00018-008-8495-2
[12] Eiden, M.V. (2008) Endogenous retroviruses--aiding and abetting genomic plasticity. Cellular and Molecular Life Sciences, 65, 3325-3328. doi:10.1007/s00018-008-8493-4
[13] Rebora, A. (2005) Human endogenous retroviruses and their possible impact on dermatology. Journal of the American Academy of Dermatology, 52, E7. doi:10.1016/S0190-9622(03)02540-4
[14] Sverdlov, E.D. (2000) Retroviruses and primate evolution. Bioessays, 22, 161-171. doi:10.1002/(SICI)1521-1878(200002)22:2<161::AID-BIES7>3.0.CO;2-X
[15] Flockerzi, A., Ruggieri, A., Frank, O., Sauter, M., Maldener, E., Kopper, B., Wullich, B., Seifarth, W., Müller- Lantzsch N., Leib-M?sch C., Meese E. and Mayer J. (2008) Expression patterns of transcribed human endogenous retrovirus herv-k (hml-2) loci in human tissues and the need for a herv transcriptome project. BMC Genomics, 9, 354. doi:10.1186/1471-2164-9-354
[16] Khodosevich, K., Lebedev, Y. and Sverdlov, E. (2002) Endogenous retroviruses and human evolution. Comparative and Functional Genomics, 3, 494-498. doi:10.1002/cfg.216
[17] Hohenadl, C., Germaier, H., Walchner, M., Hagenhofer, M., Herrmann, M., Stürzl, M., Kind, P., Hehlmann, R., Erfle, V. and Leib-M?sch, C. (1999) Transcriptional activation of endogenous retroviral sequences in human epidermal keratinocytes by UVB irradiation. Journal of Investigative Dermatology, 113, 587-594. doi:10.1046/j.1523-1747.1999.00728.x
[18] 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. doi:10.1186/1742-4690-3-44
[19] Ono, M., Kawakami, M. and Ushikubo, H. (1987) Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line t47d. Journal of Virology, 61, 2059-2062.
[20] Nelson, P.N., Hooley, P., Roden, D., Davari, E., Rylance, P., Warren, P., Martin, J. and Murray, P. G. (2004) Human endogenous retroviruses: Transposable elements with potential? Clinical and Experimental Immunology, 138, 1-9. doi:10.1111/j.1365-2249.2004.02592.x
[21] Taruscio, D. and Mantovani, A. (1998) Human endogenous retroviruses and environmental endocrine disrupters: A connection worth exploring? Teratology, 58, 27-28. doi:10.1002/(SICI)1096-9926(199808)58:2<27::AID-TERA2>3.0.CO;2-Y
[22] Schon, U., Seifarth, W., Baust, C., Hohenadl, C., Erfle, V. and Leib-M?sch, C. (2001) Cell type-specific expression and promoter activity of human endogenous retroviral long terminal repeats. Virology, 279, 280-291. doi:10.1006/viro.2000.0712
[23] Majors, J. (1990) The structure and function of retroviral long terminal repeats. Current Topics in Microbiology and Immunology, 157, 49-92. doi:10.1007/978-3-642-75218-6_3
[24] Mi, S., Lee, X., Li, X., Veldman, G.M., Finnerty, H., Racie, L., LaVallie, E., Tang, XY., Edouard, P., Howes, S., Keith, J. C. Jr. and McCoy, J. M. (2000) Syncytin is a captive retroviral envelope protein involved in human placental morpho-genesis. Nature, 403, 785-789. doi:10.1038/35001608
[25] Lower, R. (1999) The pathogenic potential of endogenous retroviruses: Facts and fantasies. Trends in Microbiology, 7, 350-356. doi:10.1016/S0966-842X(99)01565-6
[26] Dewannieux, M., Harper, F., Richaud, A., Letzelter, C., Ribet, D., Pierron, G. and Heidmann, T. (2006) Identification of an infectious progenitor for the multiplecopy herv-k human endogenous retroelements. Genome Research, 16, 1548-1556. doi:10.1101/gr.5565706
[27] Kazazian, H.H. Jr. (1998) Mobile elements and disease. Current Opinion in Genetics & Development, 8, 343-350. doi:10.1016/S0959-437X(98)80092-0
[28] Colmegna, I. and Garry, R. F. (2006) Role of endogenous retroviruses in autoimmune diseases. Infectious Disease Clinics of North America, 20, 913-929. doi:10.1016/j.idc.2006.09.008
[29] Mullins, C.S. and Linnebacher, M. (2011) Endogenous retrovirus sequences as a novel class of tumor-specific antigens: An example of HERV-H env encoding strong CTL epitopes. Cancer Immunology Immunotherapy, ahead of print. doi:10.1007/s00262-011-1183-3
[30] Buzdin, A. (2007) Human-specific endogenous retroviruses. Scientific World Journal, 7, 1848-1868. doi:10.1100/tsw.2007.270
[31] An, D. S., Xie, Y. and Chen, I. S. (2001) Envelope gene of the human endogen-ous retrovirus herv-w encodes a functional retrovirus envelope. Journal of Virology, 75, 3488-3489. doi:10.1128/JVI.75.7.3488-3489.2001
[32] Balada, E., Vilardell-Tarrés, M. and Ordi-Ros, J. (2010) Implications of human endogenous retroviruses in the development of autoimmune diseases. International Reviews of Immunology, 29, 351-370. doi:10.3109/08830185.2010.485333
[33] Lewis, D.A. (2001) Retroviruses and the pathogenesis of schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 98, 4293-4294. doi:10.1073/pnas.081075898
[34] Iturrieta-Zuazo, I. and Alelú-Paz, R. (2009) Human endogenous retroviruses, hormones and apobec3g: A connection to explore in schizophrenia. Bioscience Hypotheses, 2, 236-239. doi:10.1016/j.bihy.2009.04.006
[35] Huang, W. J., Liu, Z. C., Wei, W., Wang, G. H., Wu, J. G. and Zhu, F. (2006) Human endogenous retroviral pol rna and protein detected and identified in the blood of individuals with schizophrenia. Schizophrenia Research, 83, 193-199. doi:10.1016/j.schres.2006.01.007
[36] Katzourakis, A. and Tristem, M. (2005) Phylogeny of human endogenous and exogenous retroviruses. In: Sverdlov, E. Ed., Retro-viruses and Primate Genome Evolution, Landes Bioscience, Georgetown, 186-203.
[37] Yao, Y., Schroder, J., Nellaker, C., Bottmer, C., Bachmann, S., Yolken, R. H. and Karlsson, H. (2008) Elevated levels of human endo-genous retrovirus-w transcripts in blood cells from patients with first episode schizophrenia. Genes, Brain and Behavior, 7, 103-112.
[38] Kim, H. S., Ahn, K. and Kim, D. S. (2008) Quantitative expression of the herv-w env gene in human tissues. Archives of Virology, 153, 1587-1591. doi:10.1007/s00705-008-0159-x
[39] Karlsson, H., Bachmann, S., Schroder, J., McArthur, J., Torrey, E.F. and Yolken R.H. (2001) Retroviral rna identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 98, 4634- 4639. doi:10.1073/pnas.061021998
[40] Karlsson, H., Schroder, J., Bachmann, S., Bottmer, C., and Yolken, R.H. (2004) Herv-w-related rna detected in plasma from individuals with recent-onset schizophrenia or schizoaffective disorder. Molecular Psychiatry, 9, 12-13. doi:10.1038/sj.mp.4001439
[41] Perron, H., Mekaoui, L., Bernard, C., Veas, F., Stefas, I. and Leboyer, M. (2008) Endogenous retrovirus type w gag and envelope protein antigenemia in serum of schizophrenic patients. Biological Psychiatry, 64, 1019-1023. doi:10.1016/j.biopsych.2008.06.028
[42] Weis, S., Llenos, I.C., Sabunciyan, S., Dulay, J. R., Isler, L., Yolken, R. and Perron, H. (2007) Reduced expression of human endogenous retrovirus (herv)-w gag protein in the cingulate gyrus and hippocampus in schizophrenia, bipolar disorder, and depression. Journal of Neural Transmission, 114, 645-655. doi:10.1007/s00702-006-0599-y
[43] Frank, O., Giehl M., Zheng C., Helhmann R., Leib- M?sch C. and Seifarth W. (2005) Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders. Journal of Virology, 79, 10890-10901. doi:10.1128/JVI.79.17.10890-10901.2005
[44] Bowden, N.A., Weidenhofer, J., Scott, R.J., Schall, U., Todd, J., Michie, P.T. and Tooney, P.A. (2006) Preliminary investigation of gene expression profiles in peripheral blood lymphocytes in schizophrenia. Schizophrenia Research, 82, 175-183. doi:10.1016/j.schres.2005.11.012
[45] Serafino, A., Balestrieri, E., Pierimarchi, P., Matteucci, C., Moroni, G., Oricchio, E., Rasi, G., Mastino, A., Spadafora, C., Garaci, E. and Vallebona, P.S. (2009) The activation of human endogenous retrovirus k (herv-k) is implicated in melanoma cell malignant transformation. Experimental Cell Research, 315, 849-862. doi:10.1016/j.yexcr.2008.12.023
[46] Boller, K., Schonfeld, K., Lischer, S., Fischer, N., Hoffmann, A., Kurth, R. and T?njes, R.R. (2008) Human endogenous retrovirus herv-k113 is capable of producing intact viral particles. Journal of General Virology, 89, 567- 572. doi:10.1099/vir.0.83534-0
[47] Dickerson, F., Rubalcaba, E., Viscidi, R., Yang, S., Stallings, C., Sullens, A., Origoni, A., Leister, F. and Yolken, R. (2008) Polymorphisms in human endogenous retrovirus k-18 and risk of type 2 diabetes in individuals with schizophrenia. Schizophrenia Research, 104, 121-126. doi:10.1016/j.schres.2008.05.005
[48] Otowa, T., Tochigi, M., Rogers, M., Umekage, T., Kato, N. and Sasaki T. (2006) Insertional polymorphism of endogenous retrovirus herv-k115 in schizophrenia. Neuroscience Letters, 408, 226-229. doi:10.1016/j.neulet.2006.09.004
[49] Portis, J.L. (2002) Perspectives on the role of endogenous human retroviruses in autoimmune diseases. Virology, 296, 1-5. doi:10.1006/viro.2002.1388
[50] Leung, D.C. and Lo-rincz, M.C. (2011) Silencing of endogenous retroviruses: When and why do histone marks predominate? Trends in Biochemical Sciences, in press. doi:10.1016/j.tibs.2011.11.006
[51] Munk-Jorgensen, P. (1987) First-admission rates and marital status of schi-zophrenics. Acta Psychiatrica Scandinavica, 76, 210-216. doi:10.1111/j.1600-0447.1987.tb02886.x
[52] Wang, Z. (2009) RNA-Seq: A revolutionary tool for transcriptomics. Nature Reviews Genetics, 10, 57-63. doi:10.1038/nrg2484
[53] Wang, Z. (2009) RNA-Seq: Advances, challenges and opportunities. Nature Reviews Genetics, 12, 87-98.

  
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