Journal of the Korea Convergence Society (한국융합학회논문지)

Korea Convergence Society (한국융합학회)
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Human endogenous retroviruses and neurologic disorders

인간 내인성 레트로 바이러스와 신경학적 장애

  • Hwang, Moon-Hyon (Division of Health and Exercise Science, Incheon National University) ;
  • Sim, Young-Je (Department of Physical Education, Kunsan National University)
  • 황문현 (인천대학교 운동건강학부) ;
  • 심영제 (군산대학교 체육학과)
  • Published : 2017.06.28
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Abstract

Human endogenous retroviruses (HERVs) are fossil viruses that began to be assimilated into the human genome some 30~40 million years ago, and now constitute nearly 8% of the human genome. These ancient retroviruses have since accumulated mutations that have rendered them defective; thus, they have been termed junk DNA. However, recent research indicates that not all HERVs remain silent passengers. Although they have not been shown to be causative of any human disease, endogenous retroviral sequences may become expressed under select pathological circumstances such as neurological disorders, including multiple sclerosis (MS), schizophrenia, and Amyotrophic Lateral Sclerosis (ALS); viral infections, including human immunodeficiency virus (HIV) and herpesvirus; and multiple types of cancers. This review focused on the possible interactions of HERVs and neurological diseases.

인간 내인성 레트로 바이러스는 약 3~4 천만 년 전 인간게놈에 통합되기 시작했던 화석바이러스로서 인간게놈의 약 8%를 구성하고 있다. 이러한 고대의 레트로 바이러스는 연속된 유전자변이로 인해 본래의 기능을 잃게 됨으로써 "쓸모없는 DNA (junk DNA)"로 여겨져 왔다. 그러나 최근 연구는 모든 인간 내인성 레트로 바이러스가 단지 침묵을 지키는 승객만이 아님을 보여준다. 현재까지는 이들 바이러스가 인간 질병의 직접 원인이 된다는 것은 밝혀지지 않았으나, 다발성 경화증, 정신 분열증 및 근 위축성 측삭경화증을 포함한 신경학적 장애와 인간면 역결핍바이러스 (HIV)나 헤르페스 등의 바이러스 감염, 여러 유형의 암과 같은 질환을 가진 환자에서 인간 내인성 레트로 바이러스의 DNA가 과도발현 됨을 보여주는 연구들이 다양하게 이루어지고 있다. 이 리뷰논문은 신경학적 질환에 대한 인간 내인성 레트로 바이러스의 가능한 관련여부를 다루고 있다.

Keywords

References

  1. C. Patience, D. A. Wilkinson, & R. A. Weiss, "Our retroviral heritage", Trends Genet, Vol. 12, No. 3, pp. 116-120, 1997. https://doi.org/10.1016/0168-9525(96)81424-7
  2. D. J. Griffiths, "Endogenous retroviruses in the human genome sequence", Genome Biology, Vol. 2, No. 6, reviews 1017, 2001.
  3. W. H. Li, Z. Gu, H. Wang, & A, Nekrutenko, "Evolutionary analyses of the human genome", Nature, Vol. 409, No. 6822, pp. 847-849, 2001. https://doi.org/10.1038/35057039
  4. L. Cegolon, C. Salata, E. Weiderpass, P. Vineis, G. Palu, & G. Mastrangelo, "Human endogenous retroviruses and cancer prevention: evidence and prospects", BMC Cancer, Vol. 13, No. 4, 2013.
  5. N. Bannert, & R. Kurth, "Retroelements and the human genome: new perspectives on an old relation", Proceeding of the National Academy of Sciences of the USA, Vol. 101(Suppl. 2), pp. 14572-14579, 2004 https://doi.org/10.1073/pnas.0404838101
  6. R. Lower, J. Lower, & R. Kurth, "The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences", Proceeding of the National Academy of Sciences of the USA, Vol. 93, No. 11, pp. 5177-5184, 1996. https://doi.org/10.1073/pnas.93.11.5177
  7. G. R. Young, J. P. Stoye, & G. Kassiotis, "Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis", Bioessays, Vol. 35, No. 9, pp. 794-803, 2013. https://doi.org/10.1002/bies.201300049
  8. M. Ono, "Molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types A and B retrovirus genes", Journal of Virology, Vol. 58, No. 3, pp. 937-944, 1986.
  9. R. Lower, K. Boller, B. Hasenmaier, C. Korbmacher, N. Muller-Lantzsch, J. Lower, & R. Kurth, "Identification of human endogenous retroviruses with complex mRNA expression and particle formation", Proceeding of the National Academy of Sciences of the USA, Vol. 90, No. 10, pp. 4480-4484, 1993. https://doi.org/10.1073/pnas.90.10.4480
  10. T. Christensen, "Human endogenous retroviruses in neurologic disease", APMIS, Vol. 124, No. (1-2), pp. 116-126, 2016. https://doi.org/10.1111/apm.12486
  11. M. Sospedra, & R. Martin, "Immunology of multiple sclerosis", Annual Review of Immunology, Vol. 23, pp. 683-747, 2005. https://doi.org/10.1146/annurev.immunol.23.021704.115707
  12. S. V. Ramagopalan, R. Dobson, U. C. Meier, & G. Giovannoni, "Multiple sclerosis: risk factors, prodromes, and potential causal pathways", The Lancet. Neurology, Vol. 9, No. 7, pp. 727-739, 2010. https://doi.org/10.1016/S1474-4422(10)70094-6
  13. H. Tremlett, Y. Zhao, P. Rieckmann, & M Hutchinson, "New perspectives in the natural history of multiple sclerosis", Neurology, Vol. 74, No. 24, pp. 2004-2015, 2010. https://doi.org/10.1212/WNL.0b013e3181e3973f
  14. J. B. Johnston, C. Silva, J. Holden, K. G. Warren, A. W. Clark, & C. Power, "Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases", Annals of Neurology, Vol. 50, No. 4, pp. 434-442, 2001. https://doi.org/10.1002/ana.1131
  15. J. M. Antony, K. K. Ellestad, R. Hammond, K. Imaizumi, F. Mallet, K. G. Warren, & C. Power, "The human endogenous retrovirus envelope glycoprotein, syncytin-1, regulates neuroinflammation and its receptor expression in multiple sclerosis: a role for endoplasmic reticulum chaperones in astrocytes", Journal of Immunology, Vol. 179, No. 2, pp. 1210-1224, 2007. https://doi.org/10.4049/jimmunol.179.2.1210
  16. H. Perron, F. Lazarini, K. Ruprecht, C. Pechoux-Longin, D. Seilhean, V. Sazodovitch, A. Creange, N. Battail-Poirot, G. Sibai, L. Santoro, M. Jolivet, J. L. Darlix, P. Rieckmann, T. Arzberger, J. J. Hauw, & H. Lassmann, "Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions", Journal of Neurovirology, Vol. 11, No. 1, pp. 23-33, 2005. https://doi.org/10.1080/13550280590901741
  17. J. M. Antony, A. M. Deslauriers, R. K. Bhat, K. K. Ellestad, & C. Power, "Human endogenous retroviruses and multiple sclerosis: innocent bystanders or disease determinants?", Biochimica et Biophysica Acta, Vol. 1812, No. 2, pp. 162-176, 2011. https://doi.org/10.1016/j.bbadis.2010.07.016
  18. T. Christensen, P. D. Sorensen, H. J. Hansen, & A. Moller-Larsen, "Antibodies against a human endogenous retrovirus and the preponderance of env splice variants in multiple sclerosis patients", Multiple Sclerosis, Vol. 9, No. 1, pp. 6-15, 2003. https://doi.org/10.1191/1352458503ms867oa
  19. T. Brudek, T. Christensen, L. Aagaard, T. Petersen, H. J. Hansen, & A. Moller-Larsen, "B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity", Retrovirology, Vol. 6, 2009.
  20. A. K. Tai, E. J. O'Reilly, K. A. Alroy, K. C. Simon, K. L. Munger, B. T. Huber, & A. Ascherio, "Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis", Multiple Sclerosis, Vol. 14, No. 9, pp. 1175-1180, 2008. https://doi.org/10.1177/1352458508094641
  21. R. Tandon, M. S. Keshavan, & H. A. Nasrallah, "Schizophrenia, "just the facts" what we know in 2008. 2. Epidemiology and etiology", Schizophrenia Research, Vol. 102, No. (1-3), pp. 1-18, 2008.
  22. H. Hegyi, "GABBR1 has a HERV-W LTR in its regulatory region--a possible implication for schizophrenia", Biology Direct, Vol. 8, 2013.
  23. A. E. Pulver, "Search for schizophrenia susceptibility genes", Biological Psychiatry, Vol. 47, No. 3, pp. 221-230, 2000. https://doi.org/10.1016/S0006-3223(99)00281-4
  24. M. Tsuang, "Schizophrenia: genes and environment", Biological Psychiatry, Vol. 47, No. 3, pp. 210-220, 2000. https://doi.org/10.1016/S0006-3223(99)00289-9
  25. R. H. Yolken, H. Karlsson, F. Yee, N. L. Johnston-Wilson, & E. F. Torrey, "Endogenous retroviruses and schizophrenia", Brain Research. Brain Research Review, Vol. 31, No. (2-3), pp. 193-199, 2000.
  26. H. Karlsson, S. Bachmann, J. Schroder, J. McArthur, E. F. Torrey, & R. H. Yolken, "Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia", Proceeding of the National Academy of Sciences of the USA, Vol. 98, No. 8, pp. 4634-4639, 2001. https://doi.org/10.1073/pnas.061021998
  27. H. Karlsson, J. Schroder, S. Bachmann, C. Bottmer, & R. H. Yolken, "HERV-W-related RNA detected in plasma from individuals with recent-onset schizophrenia or schizoaffective disorder", Molecular Psychiatry, Vol. 9, No. 1, pp. 12-13, 2004. https://doi.org/10.1038/sj.mp.4001439
  28. W. Huang, S. Li, Y. Hu, H. Yu, F. Luo, Q. Zhang, & F. Zhu, "Implication of the env gene of the HERV-W family in the expression of BDNF and DRD3 and development of recent-onset schizophrenia", Schizophrenia Bulletin, Vol. 37, No, 5, pp. 988-1000, 2010. https://doi.org/10.1093/schbul/sbp166
  29. O. Frank, M. Giehl, C. Zheng, R. Hehlmann, C. Leib-Mosch, & W. Seifarth, "Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders", Journal of Virology, Vol. 79, No. 17, pp. 10890-10901, 2005. https://doi.org/10.1128/JVI.79.17.10890-10901.2005
  30. S. Ajroud-Driss, & T. Siddique. "Sporadic and hereditary amyotrophic lateral sclerosis(ALS)", Biochimica et Biophysica Acta, Vol. 1852, No. 4, pp. 679-684, 2015. https://doi.org/10.1016/j.bbadis.2014.08.010
  31. T. Alfahad, & A. Nath, "Retroviruses and amyotrophic lateral sclerosis", Antiviral Research, Vol. 99, No. (2), pp. 180-187, 2016. https://doi.org/10.1016/j.antiviral.2013.05.006
  32. F. Navone, P. Genevini, & N. Borgese, "Autophagy and Neurodegeneration: Insights from a Cultured Cell Model of ALSS", Cells, Vol. 4, No. 3, pp. 354-486, 2015. https://doi.org/10.3390/cells4030354
  33. S. Vucic, & M. C. Kiernan, "Pathophysiology of neurodegeneration in familial amyotrophic lateral sclerosis", Current Molecular Medicine, Vol. 9, No. 3, pp. 255-272, 2009. https://doi.org/10.2174/156652409787847173
  34. A. Verma, & J. R. Berger, "ALS syndrome in patients with HIV-1 infection", Journal of the Neurological Sciences, Vol. 240, No. (1-2), pp. 59-64, 2006. https://doi.org/10.1016/j.jns.2005.09.005
  35. A. Moulignier, A. Moulonguet, G. Pialoux, & W. Rozenbaum, "Reversible ALS-like disorder in HIV infection", Neurology, Vol. 57, No. 6, pp. 995-1001, 2001. https://doi.org/10.1212/WNL.57.6.995
  36. P. Jolicoeur, "Neuronal loss in a lower motor neuron disease induced by a murine retrovirus", The Canadian Journal of Neurological Sciences, Vol. 18, No. (3 Suppl), pp. 411-413, 1991. https://doi.org/10.1017/S031716710003256X
  37. A. L. McCormick, R. H. Jr Brown, M. E. Cudkowicz, A. Al-Chalabi, & J. A. Garson, "Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate", Neurology, Vol. 70, No. 4, pp. 278-283, 2008. https://doi.org/10.1212/01.wnl.0000297552.13219.b4
  38. R. Douville, J. Liu, J. Rothstein, & A. Nath, "Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis", Annals Neurology, Vol. 69, No. 1, pp. 141-151, 2011. https://doi.org/10.1002/ana.22149