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Molecular functions of human endogenous retroviruses in health and disease

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Abstract

Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8 % of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

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References

  1. Buzdin A, Kovalskaya-Alexandrova E, Gogvadze E, Sverdlov E (2006) At least 50 % of human-specific HERV-K (HML-2) long terminal repeats serve in vivo as active promoters for host nonrepetitive DNA transcription. J Virol 80(21):10752–10762

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Li F, Nellåker C, Sabunciyan S, Yolken RH, Jones-Brando L, Johansson A-S, Br Owe-Larsson, Karlsson H (2014) Transcriptional derepression of the ERVWE1 locus following influenza A virus infection. J Virol 88(8):4328–4337

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Fuchs NV, Loewer S, Daley GQ, Izsvak Z, Lower J, Lower R (2013) Human endogenous retrovirus K (HML-2) RNA and protein expression is a marker for human embryonic and induced pluripotent stem cells. Retrovirology 10:115

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Suntsova M, Gogvadze EV, Salozhin S, Gaifullin N, Eroshkin F, Dmitriev SE, Martynova N, Kulikov K, Malakhova G, Tukhbatova G, Bolshakov AP, Ghilarov D, Garazha A, Aliper A, Cantor CR, Solokhin Y, Roumiantsev S, Balaban P, Zhavoronkov A, Buzdin A (2013) Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked gene PRODH. Proc Natl Acad Sci USA 110(48):19472–19477

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Chuong EB, Rumi MA, Soares MJ, Baker JC (2013) Endogenous retroviruses function as species-specific enhancer elements in the placenta. Nat Genet 45(3):325–329

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Kim HS (2012) Genomic impact, chromosomal distribution and transcriptional regulation of HERV elements. Mol Cells 33(6):539–544

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Yu HL, Zhao ZK, Zhu F (2013) The role of human endogenous retroviral long terminal repeat sequences in human cancer (review). Int J Mol Med 32(4):755–762

    CAS  PubMed  Google Scholar 

  8. Schumann GG, Gogvadze EV, Osanai-Futahashi M, Kuroki A, Munk C, Fujiwara H, Ivics Z, Buzdin AA (2010) Unique functions of repetitive transcriptomes. Int Rev Cell Mol Biol 285:115–188

    Article  CAS  PubMed  Google Scholar 

  9. Ling J, Pi W, Yu X, Bengra C, Long Q, Jin H, Seyfang A, Tuan D (2003) The ERV-9 LTR enhancer is not blocked by the HS5 insulator and synthesizes through the HS5 site non-coding, long RNAs that regulate LTR enhancer function. Nucleic Acids Res 31(15):4582–4596

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Gogvadze E, Buzdin A (2009) Retroelements and their impact on genome evolution and functioning. Cell Mol Life Sci CMLS 66(23):3727–3742

    Article  CAS  PubMed  Google Scholar 

  11. Tarumi C, Matsunuma N, Miyakoshi N, Yamashita K, Masuda H (1989) Long term oral administration study of pravastatin sodium to beagles for 104 weeks. J Toxicol Sci 14(Suppl 1):85–101

    Article  CAS  PubMed  Google Scholar 

  12. Young JM, Whiddon JL, Yao Z, Kasinathan B, Snider L, Geng LN, Balog J, Tawil R, van der Maarel SM, Tapscott SJ (2013) DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis. PLoS Genet 9(11):e1003947

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Arjan-Odedra S, Swanson CM, Sherer NM, Wolinsky SM, Malim MH (2012) Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses. Retrovirology 9:53

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Maliniemi P, Vincendeau M, Mayer J, Frank O, Hahtola S, Karenko L, Carlsson E, Mallet F, Seifarth W, Leib-Mosch C, Ranki A (2013) Expression of human endogenous retrovirus-w including syncytin-1 in cutaneous T-cell lymphoma. PLoS ONE 8(10):e76281

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Zhang Y, Babaian A, Gagnier L, Mager DL (2013) Visualized computational predictions of transcriptional effects by intronic endogenous retroviruses. PLoS ONE 8(8):e71971

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Gosenca D, Gabriel U, Steidler A, Mayer J, Diem O, Erben P, Fabarius A, Leib-Mosch C, Hofmann WK, Seifarth W (2012) HERV-E-mediated modulation of PLA2G4A transcription in urothelial carcinoma. PLoS ONE 7(11):e49341

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Triviai I, Ziegler M, Bergholz U, Oler AJ, Stubig T, Prassolov V, Fehse B, Kozak CA, Kroger N, Stocking C (2014) Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis. Proc Natl Acad Sci USA 111(23):8595–8600

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Sverdlov ED (2000) Retroviruses and primate evolution. BioEssays: news and reviews in molecular, cellular and developmental biology 22(2):161–171

    Article  CAS  Google Scholar 

  19. Buzdin A (2007) Human-specific endogenous retroviruses. Sci World J 7:1848–1868

    Article  CAS  Google Scholar 

  20. Belshaw R, Pereira V, Katzourakis A, Talbot G, Paces J, Burt A, Tristem M (2004) Long-term reinfection of the human genome by endogenous retroviruses. Proc Natl Acad Sci USA 101(14):4894–4899

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Romano CM, Ramalho RF, Zanotto PM (2006) Tempo and mode of ERV-K evolution in human and chimpanzee genomes. Arch Virol 151(11):2215–2228

    Article  CAS  PubMed  Google Scholar 

  22. Hohn O, Hanke K, Bannert N (2013) HERV-K(HML-2), the best preserved family of HERVs: endogenization, expression, and implications in health and disease. Front Oncol 3:246

    Article  PubMed Central  PubMed  Google Scholar 

  23. Dewannieux M, Heidmann T (2013) Endogenous retroviruses: acquisition, amplification and taming of genome invaders. Curr Opin Virol 3(6):646–656

    Article  CAS  PubMed  Google Scholar 

  24. Buzdin A, Ustyugova S, Khodosevich K, Mamedov I, Lebedev Y, Hunsmann G, Sverdlov E (2003) Human-specific subfamilies of HERV-K (HML-2) long terminal repeats: three master genes were active simultaneously during branching of hominoid lineages. Genomics 81(2):149–156

    Article  CAS  PubMed  Google Scholar 

  25. Wildschutte JH, Ram D, Subramanian R, Stevens VL, Coffin JM (2014) The distribution of insertionally polymorphic endogenous retroviruses in breast cancer patients and cancer-free controls. Retrovirology 11:62

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Ruda VM, Akopov SB, Trubetskoy DO, Manuylov NL, Vetchinova AS, Zavalova LL, Nikolaev LG, Sverdlov ED (2004) Tissue specificity of enhancer and promoter activities of a HERV-K(HML-2) LTR. Virus Res 104(1):11–16

    Article  CAS  PubMed  Google Scholar 

  27. Kovalskaya E, Buzdin A, Gogvadze E, Vinogradova T, Sverdlov E (2006) Functional human endogenous retroviral LTR transcription start sites are located between the R and U5 regions. Virology 346(2):373–378

    Article  CAS  PubMed  Google Scholar 

  28. van de Lagemaat LN, Landry JR, Mager DL, Medstrand P (2003) Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet 19(10):530–536

    Article  PubMed  CAS  Google Scholar 

  29. Hughes JF, Coffin JM (2004) Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: implications for human and viral evolution. Proc Natl Acad Sci USA 101(6):1668–1672

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Buzdin AA, Lebedev IuB, Sverdlov ED (2003) Human genome-specific HERV-K intron LTR genes have a random orientation relative to the direction of transcription, and possibly, participated in antisense gene expression regulation. Bioorg Khim 29(1):103–106

    CAS  PubMed  Google Scholar 

  31. Mayer J, Stuhr T, Reus K, Maldener E, Kitova M, Asmus F, Meese E (2005) Haplotype analysis of the human endogenous retrovirus locus HERV-K(HML-2.HOM) and its evolutionary implications. J Mol Evol 61(5):706–715

    Article  CAS  PubMed  Google Scholar 

  32. Seifarth W, Frank O, Zeilfelder U, Spiess B, Greenwood AD, Hehlmann R, Leib-Mosch C (2005) Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray. J Virol 79(1):341–352

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Lyden TW, Johnson PM, Mwenda JM, Rote NS (1994) Ultrastructural characterization of endogenous retroviral particles isolated from normal human placentas. Biol Reprod 51(1):152–157

    Article  CAS  PubMed  Google Scholar 

  34. Medstrand P, Blomberg J (1993) Characterization of novel reverse transcriptase encoding human endogenous retroviral sequences similar to type A and type B retroviruses: differential transcription in normal human tissues. J Virol 67(11):6778–6787

    PubMed Central  CAS  PubMed  Google Scholar 

  35. Cho K, Lee YK, Greenhalgh DG (2008) Endogenous retroviruses in systemic response to stress signals. Shock 30(2):105–116

    Article  CAS  PubMed  Google Scholar 

  36. Campbell IM, Gambin T, Dittwald P, Beck CR, Shuvarikov A, Hixson P, Patel A, Gambin A, Shaw CA, Rosenfeld JA, Stankiewicz P (2014) Human endogenous retroviral elements promote genome instability via non-allelic homologous recombination. BMC Biol 12:74

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Bannert N, Kurth R (2004) Retroelements and the human genome: new perspectives on an old relation. Proc Natl Acad Sci USA 101(Suppl 2):14572–14579

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Medstrand P, Mager DL (1998) Human-specific integrations of the HERV-K endogenous retrovirus family. J Virol 72(12):9782–9787

    PubMed Central  CAS  PubMed  Google Scholar 

  39. Lavie L, Kitova M, Maldener E, Meese E, Mayer J (2005) CpG methylation directly regulates transcriptional activity of the human endogenous retrovirus family HERV-K(HML-2). J Virol 79(2):876–883

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Khodosevich KV, Lebedev IuB, Sverdlov ED (2004) The tissue-specific methylation of human-specific endogenous retroviral long terminal repeats. Bioorg Khim 30(5):493–498

    CAS  PubMed  Google Scholar 

  41. Khodosevich K, Lebedev Y, Sverdlov ED (2004) Large-scale determination of the methylation status of retrotransposons in different tissues using a methylation tags approach. Nucleic Acids Res 32(3):e31

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Akopov SB, Nikolaev LG, Khil PP, Lebedev YB, Sverdlov ED (1998) Long terminal repeats of human endogenous retrovirus K family (HERV-K) specifically bind host cell nuclear proteins. FEBS Lett 421(3):229–233

    Article  CAS  PubMed  Google Scholar 

  43. Trubetskoy DO, Zavalova LL, Akopov SB, Nikolaev LG (2002) Purification of proteins specifically binding human endogenous retrovirus K long terminal repeat by affinity elution chromatography. J Chromatogr A 976(1–2):95–101

    Article  CAS  PubMed  Google Scholar 

  44. Domansky AN, Kopantzev EP, Snezhkov EV, Lebedev YB, Leib-Mosch C, Sverdlov ED (2000) Solitary HERV-K LTRs possess bi-directional promoter activity and contain a negative regulatory element in the U5 region. FEBS Lett 472(2–3):191–195

    Article  CAS  PubMed  Google Scholar 

  45. Vinogradova TV, Leppik LP, Nikolaev LG, Akopov SB, Kleiman AM, Senyuta NB, Sverdlov ED (2001) Solitary human endogenous retroviruses-K LTRs retain transcriptional activity in vivo, the mode of which is different in different cell types. Virology 290(1):83–90

    Article  CAS  PubMed  Google Scholar 

  46. Vinogradova T, Leppik L, Kalinina E, Zhulidov P, Grzeschik KH, Sverdlov E (2002) Selective Differential Display of RNAs containing interspersed repeats: analysis of changes in the transcription of HERV-K LTRs in germ cell tumors. Mol Genet Genomics 266(5):796–805

    Article  CAS  PubMed  Google Scholar 

  47. Buzdin A, Kovalskaya-Alexandrova E, Gogvadze E, Sverdlov E (2006) GREM, a technique for genome-wide isolation and quantitative analysis of promoter active repeats. Nucleic Acids Res 34(9):e67

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Gogvadze E, Stukacheva E, Buzdin A, Sverdlov E (2009) Human-specific modulation of transcriptional activity provided by endogenous retroviral insertions. J Virol 83(12):6098–6105. doi:10.1128/JVI.00123-09

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Buzdin AA (2004) Retroelements and formation of chimeric retrogenes. Cell Mol Life Sci CMLS 61(16):2046–2059

    Article  CAS  PubMed  Google Scholar 

  50. Mack M, Bender K, Schneider PM (2004) Detection of retroviral antisense transcripts and promoter activity of the HERV-K(C4) insertion in the MHC class III region. Immunogenetics 56(5):321–332

    Article  CAS  PubMed  Google Scholar 

  51. Sverdlov ED (1999) Retroviral regulators of gene expression in the human genome as possible factors for its evolution. Bioorg Khim 25(11):821–827

    CAS  PubMed  Google Scholar 

  52. Dewannieux M, Harper F, Richaud A, Letzelter C, Ribet D, Pierron G, Heidmann T (2006) Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res 16(12):1548–1556

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Lee YN, Bieniasz PD (2007) Reconstitution of an infectious human endogenous retrovirus. PLoS Pathog 3(1):e10

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Kandel ES, Nudler E (2002) Template switching by RNA polymerase II in vivo. Evidence and implications from a retroviral system. Mol Cell 10(6):1495–1502

    Article  CAS  PubMed  Google Scholar 

  55. Coffin JM (1990) Molecular mechanisms of nucleic acid integration. J Med Virol 31(1):43–49

    Article  CAS  PubMed  Google Scholar 

  56. Coffin JM (1996) Retroviridae: the viruses and their replication. Fields virology. Lippincott-Raven Publishers, Philadelphia

    Google Scholar 

  57. Boller K, Konig H, Sauter M, Mueller-Lantzsch N, Lower R, Lower J, Kurth R (1993) Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. Virology 196(1):349–353. doi:10.1006/viro.1993.1487

    Article  CAS  PubMed  Google Scholar 

  58. Lower R, Tonjes RR, Korbmacher C, Kurth R, Lower J (1995) Identification of a Rev-related protein by analysis of spliced transcripts of the human endogenous retroviruses HTDV/HERV-K. J Virol 69(1):141–149

    PubMed Central  CAS  PubMed  Google Scholar 

  59. Armbruester V, Sauter M, Roemer K, Best B, Hahn S, Nty A, Schmid A, Philipp S, Mueller A, Mueller-Lantzsch N (2004) Np9 protein of human endogenous retrovirus K interacts with ligand of numb protein X. J Virol 78(19):10310–10319. doi:10.1128/JVI.78.19.10310-10319.2004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Armbruester V, Sauter M, Krautkraemer E, Meese E, Kleiman A, Best B, Roemer K, Mueller-Lantzsch N (2002) A novel gene from the human endogenous retrovirus K expressed in transformed cells. Clin Cancer Res 8(6):1800–1807

    CAS  PubMed  Google Scholar 

  61. Magin C, Lower R, Lower J (1999) cORF and RcRE, the Rev/Rex and RRE/RxRE homologues of the human endogenous retrovirus family HTDV/HERV-K. J Virol 73(11):9496–9507

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Hanke K, Hohn O, Liedgens L, Fiddeke K, Wamara J, Kurth R, Bannert N (2013) Staufen-1 interacts with the human endogenous retrovirus family HERV-K(HML-2) rec and gag proteins and increases virion production. J Virol 87(20):11019–11030

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Magin-Lachmann C, Hahn S, Strobel H, Held U, Lower J, Lower R (2001) Rec (formerly Corf) function requires interaction with a complex, folded RNA structure within its responsive element rather than binding to a discrete specific binding site. J Virol 75(21):10359–10371

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Kleiman A, Senyuta N, Tryakin A, Sauter M, Karseladze A, Tjulandin S, Gurtsevitch V, Mueller-Lantzsch N (2004) HERV-K(HML-2) GAG/ENV antibodies as indicator for therapy effect in patients with germ cell tumors. Int J Cancer 110(3):459–461

    Article  CAS  PubMed  Google Scholar 

  65. Wang-Johanning F, Liu J, Rycaj K, Huang M, Tsai K, Rosen DG, Chen DT, Lu DW, Barnhart KF, Johanning GL (2007) Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer. Int J Cancer 120(1):81–90

    Article  CAS  PubMed  Google Scholar 

  66. Herve CA, Lugli EB, Brand A, Griffiths DJ, Venables PJ (2002) Autoantibodies to human endogenous retrovirus-K are frequently detected in health and disease and react with multiple epitopes. Clin Exp Immunol 128(1):75–82

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Ono M, Kawakami M, Ushikubo H (1987) Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line T47D. J Virol 61(6):2059–2062

    PubMed Central  CAS  PubMed  Google Scholar 

  68. Andersson AC, Svensson AC, Rolny C, Andersson G, Larsson E (1998) Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues. Int J Oncol 12(2):309–313

    CAS  PubMed  Google Scholar 

  69. Hugin AW, Vacchio MS, Morse HC 3rd (1991) A virus-encoded “superantigen” in a retrovirus-induced immunodeficiency syndrome of mice. Science 252(5004):424–427

    Article  CAS  PubMed  Google Scholar 

  70. Mayer J, Meese EU (2003) Presence of dUTPase in the various human endogenous retrovirus K (HERV-K) families. J Mol Evol 57(6):642–649

    Article  CAS  PubMed  Google Scholar 

  71. Harris JM, McIntosh EM, Muscat GE (2000) Expression and cytoplasmic localisation of deoxyuridine triphosphate pyrophosphatase encoded by a human endogenous retrovirus. Arch Virol 145(2):353–363

    Article  CAS  PubMed  Google Scholar 

  72. Harris JM, McIntosh EM, Muscat GE (1999) Structure/function analysis of a dUTPase: catalytic mechanism of a potential chemotherapeutic target. J Mol Biol 288(2):275–287

    Article  CAS  PubMed  Google Scholar 

  73. Boese A, Galli U, Geyer M, Sauter M, Mueller-Lantzsch N (2001) The Rev/Rex homolog HERV-K cORF multimerizes via a C-terminal domain. FEBS Lett 493(2–3):117–121

    Article  CAS  PubMed  Google Scholar 

  74. Galli UM, Sauter M, Lecher B, Maurer S, Herbst H, Roemer K, Mueller-Lantzsch N (2005) Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors. Oncogene 24(19):3223–3228. doi:10.1038/sj.onc.1208543

    Article  CAS  PubMed  Google Scholar 

  75. Denner J, Persin C, Vogel T, Haustein D, Norley S, Kurth R (1996) The immunosuppressive peptide of HIV-1 inhibits T and B lymphocyte stimulation. J Acquir Immune Defic Syndr Hum Retrovirol 12(5):442–450

    Article  CAS  PubMed  Google Scholar 

  76. Morozov VA, Dao Thi VL, Denner J (2013) The transmembrane protein of the human endogenous retrovirus-K (HERV-K) modulates cytokine release and gene expression. PLoS ONE 8(8):e70399

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Melder DC, Pankratz VS, Federspiel MJ (2003) Evolutionary pressure of a receptor competitor selects different subgroup a avian leukosis virus escape variants with altered receptor interactions. J Virol 77(19):10504–10514

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Brinzevich D, Young GR, Sebra R, Ayllon J, Maio SM, Deikus G, Chen BK, Fernandez-Sesma A, Simon V, Mulder LC (2014) HIV-1 interacts with human endogenous retrovirus K (HML-2) envelopes derived from human primary lymphocytes. J Virol 88(11):6213–6223

    Article  PubMed Central  PubMed  Google Scholar 

  79. Belshaw R, Dawson AL, Woolven-Allen J, Redding J, Burt A, Tristem M (2005) Genomewide screening reveals high levels of insertional polymorphism in the human endogenous retrovirus family HERV-K(HML2): implications for present-day activity. J Virol 79(19):12507–12514

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Buzdin A, Khodosevich K, Mamedov I, Vinogradova T, Lebedev Y, Hunsmann G, Sverdlov E (2002) A technique for genome-wide identification of differences in the interspersed repeats integrations between closely related genomes and its application to detection of human-specific integrations of HERV-K LTRs. Genomics 79(3):413–422

    Article  CAS  PubMed  Google Scholar 

  81. Lebedev YB, Belonovitch OS, Zybrova NV, Khil PP, Kurdyukov SG, Vinogradova TV, Hunsmann G, Sverdlov ED (2000) Differences in HERV-K LTR insertions in orthologous loci of humans and great apes. Gene 247(1–2):265–277

    Article  CAS  PubMed  Google Scholar 

  82. Lavrentieva I, Khil P, Vinogradova T, Akhmedov A, Lapuk A, Shakhova O, Lebedev Y, Monastyrskaya G, Sverdlov ED (1998) Subfamilies and nearest-neighbour dendrogram for the LTRs of human endogenous retroviruses HERV-K mapped on human chromosome 19: physical neighbourhood does not correlate with identity level. Hum Genet 102(1):107–116

    Article  CAS  PubMed  Google Scholar 

  83. Mamedov I, Batrak A, Buzdin A, Arzumanyan E, Lebedev Y, Sverdlov ED (2002) Genome-wide comparison of differences in the integration sites of interspersed repeats between closely related genomes. Nucleic Acids Res 30(14):e71

    Article  PubMed Central  PubMed  Google Scholar 

  84. Buzdin A, Vinogradova T, Lebedev Y, Sverdlov E (2005) Genome-wide experimental identification and functional analysis of human specific retroelements. Cytogenet Genome Res 110(1–4):468–474

    Article  CAS  PubMed  Google Scholar 

  85. Barbulescu M, Turner G, Seaman MI, Deinard AS, Kidd KK, Lenz J (1999) Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans. Curr Biol 9(16):861–868

    Article  CAS  PubMed  Google Scholar 

  86. Turner G, Barbulescu M, Su M, Jensen-Seaman MI, Kidd KK, Lenz J (2001) Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr Biol 11(19):1531–1535

    Article  CAS  PubMed  Google Scholar 

  87. Tristem M (2000) Identification and characterization of novel human endogenous retrovirus families by phylogenetic screening of the human genome mapping project database. J Virol 74(8):3715–3730

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Lower R, Lower J, Kurth R (1996) The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc Natl Acad Sci USA 93(11):5177–5184

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Dewannieux M, Blaise S, Heidmann T (2005) Identification of a functional envelope protein from the HERV-K family of human endogenous retroviruses. J Virol 79(24):15573–15577

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Frank O, Giehl M, Zheng C, Hehlmann R, Leib-Mosch C, Seifarth W (2005) Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders. J Virol 79(17):10890–10901

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Macfarlane C, Simmonds P (2004) Allelic variation of HERV-K(HML-2) endogenous retroviral elements in human populations. J Mol Evol 59(5):642–656

    Article  CAS  PubMed  Google Scholar 

  92. Mamedov I, Lebedev Y, Hunsmann G, Khusnutdinova E, Sverdlov E (2004) A rare event of insertion polymorphism of a HERV-K LTR in the human genome. Genomics 84(3):596–599

    Article  CAS  PubMed  Google Scholar 

  93. Marchi E, Kanapin A, Magiorkinis G, Belshaw R (2014) Unfixed endogenous retroviral insertions in the human population. J Virol 88(17):9529–9537. doi:10.1128/JVI.00919-14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  94. Kahyo T, Tao H, Shinmura K, Yamada H, Mori H, Funai K, Kurabe N, Suzuki M, Tanahashi M, Niwa H, Ogawa H, Tanioka F, Yin G, Morita M, Matsuo K, Kono S, Sugimura H (2013) Identification and association study with lung cancer for novel insertion polymorphisms of human endogenous retrovirus. Carcinogenesis 34(11):2531–2538. doi:10.1093/carcin/bgt253

    Article  CAS  PubMed  Google Scholar 

  95. Rakoff-Nahoum S, Kuebler PJ, Heymann JJ, E Sheehy M, Ortiz GM, S Ogg G, Barbour JD, Lenz J, Steinfeld AD, Nixon DF (2006) Detection of T lymphocytes specific for human endogenous retrovirus K (HERV-K) in patients with seminoma. AIDS Res Hum Retroviruses 22(1):52–56. doi:10.1089/aid.2006.22.52

    Article  CAS  PubMed  Google Scholar 

  96. Denner J (2015) Xenotransplantation and hepatitis E virus. Xenotransplantation. doi:10.1111/xen.12156

    Google Scholar 

  97. Fiebig U, Keller M, Moller A, Timms P, Denner J (2015) Lack of antiviral antibody response in koalas infected with koala retroviruses (KoRV). Virus Res 198:30–34. doi:10.1016/j.virusres.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  98. Kassiotis G (2014) Endogenous retroviruses and the development of cancer. J Immunol 192(4):1343–1349. doi:10.4049/jimmunol.1302972

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Contreras-Galindo R, Kaplan MH, He S, Contreras-Galindo AC, Gonzalez-Hernandez MJ, Kappes F, Dube D, Chan SM, Robinson D, Meng F, Dai M, Gitlin SD, Chinnaiyan AM, Omenn GS, Markovitz DM (2013) HIV infection reveals widespread expansion of novel centromeric human endogenous retroviruses. Genome Res 23(9):1505–1513. doi:10.1101/gr.144303.112

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. de Parseval N, Diop G, Blaise S, Helle F, Vasilescu A, Matsuda F, Heidmann T (2005) Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: genes and pseudogenes. BMC Genomics 6:117. doi:10.1186/1471-2164-6-117

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  101. Brosius J (1999) RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements. Gene 238(1):115–134

    Article  CAS  PubMed  Google Scholar 

  102. Leib-Mosch C, Haltmeier M, Werner T, Geigl EM, Brack-Werner R, Francke U, Erfle V, Hehlmann R (1993) Genomic distribution and transcription of solitary HERV-K LTRs. Genomics 18(2):261–269. doi:10.1006/geno.1993.1464

    Article  CAS  PubMed  Google Scholar 

  103. Hohenadl C, Leib-Mosch C, Hehlmann R, Erfle V (1996) Biological significance of human endogenous retroviral sequences. J Acqui Immune Defic Syndr Hum Retrovirol 13(Suppl 1):S268–S273

    Article  Google Scholar 

  104. Perot P, Cheynet V, Decaussin-Petrucci M, Oriol G, Mugnier N, Rodriguez-Lafrasse C, Ruffion A, Mallet F (2013) Microarray-based identification of individual HERV loci expression: application to biomarker discovery in prostate cancer. J Vis Exp 81:e50713. doi:10.3791/50713

    PubMed  Google Scholar 

  105. Jacques PE, Jeyakani J, Bourque G (2013) The majority of primate-specific regulatory sequences are derived from transposable elements. PLoS Genet 9(5):e1003504. doi:10.1371/journal.pgen.1003504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Ho B, Baker PM, Singh S, Shih SJ, Vaughan AT (2012) Localized DNA cleavage secondary to genotoxic exposure adjacent to an Alu inverted repeat. Genes Chromosom Cancer 51(5):501–509. doi:10.1002/gcc.21938

    Article  CAS  PubMed  Google Scholar 

  107. Garazha A, Ivanova A, Suntsova M, Malakhova G, Roumiantsev S, Zhavoronkov A, Buzdin A (2015) New bioinformatic tool for quick identification of functionally relevant endogenous retroviral inserts in human genome. Cell Cycle 14:1476–1484

    Article  PubMed  CAS  Google Scholar 

  108. Meisler MH, Ting CN (1993) The remarkable evolutionary history of the human amylase genes. Crit Rev Oral Biol Med 4(3–4):503–509

    CAS  PubMed  Google Scholar 

  109. Conley AB, Piriyapongsa J, Jordan IK (2008) Retroviral promoters in the human genome. Bioinformatics 24(14):1563–1567. doi:10.1093/bioinformatics/btn243

    Article  CAS  PubMed  Google Scholar 

  110. van de Lagemaat LN, Medstrand P, Mager DL (2006) Multiple effects govern endogenous retrovirus survival patterns in human gene introns. Genome Biol 7(9):R86. doi:10.1186/gb-2006-7-9-r86

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  111. Cutter AD, Good JM, Pappas CT, Saunders MA, Starrett DM, Wheeler TJ (2005) Transposable element orientation bias in the Drosophila melanogaster genome. J Mol Evol 61(6):733–741. doi:10.1007/s00239-004-0243-0

    Article  CAS  PubMed  Google Scholar 

  112. Baust C, Seifarth W, Germaier H, Hehlmann R, Leib-Mosch C (2000) HERV-K-T47D-Related long terminal repeats mediate polyadenylation of cellular transcripts. Genomics 66(1):98–103. doi:10.1006/geno.2000.6175

    Article  CAS  PubMed  Google Scholar 

  113. Kuryshev VY, Vorobyov E, Zink D, Schmitz J, Rozhdestvensky TS, Munstermann E, Ernst U, Wellenreuther R, Moosmayer P, Bechtel S, Schupp I, Horst J, Korn B, Poustka A, Wiemann S (2006) An anthropoid-specific segmental duplication on human chromosome 1q22. Genomics 88(2):143–151. doi:10.1016/j.ygeno.2006.02.002

    Article  CAS  PubMed  Google Scholar 

  114. Kjellman C, Sjogren HO, Salford LG, Widegren B (1999) HERV-F (XA34) is a full-length human endogenous retrovirus expressed in placental and fetal tissues. Gene 239(1):99–107

    Article  CAS  PubMed  Google Scholar 

  115. Mager DL, Hunter DG, Schertzer M, Freeman JD (1999) Endogenous retroviruses provide the primary polyadenylation signal for two new human genes (HHLA2 and HHLA3). Genomics 59(3):255–263. doi:10.1006/geno.1999.5877

    Article  CAS  PubMed  Google Scholar 

  116. Maeda N (1985) Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair. The haptoglobin-related gene contains a retrovirus-like element. J Biol Chem 260(11):6698–6709

    CAS  PubMed  Google Scholar 

  117. Hatada S, Grant DJ, Maeda N (2003) An intronic endogenous retrovirus-like sequence attenuates human haptoglobin-related gene expression in an orientation-dependent manner. Gene 319:55–63

    Article  CAS  PubMed  Google Scholar 

  118. Maeda N, Kim HS (1990) Three independent insertions of retrovirus-like sequences in the haptoglobin gene cluster of primates. Genomics 8(4):671–683

    Article  CAS  PubMed  Google Scholar 

  119. Turelli P, Castro-Diaz N, Marzetta F, Kapopoulou A, Raclot C, Duc J, Tieng V, Quenneville S, Trono D (2014) Interplay of TRIM28 and DNA methylation in controlling human endogenous retroelements. Genome Res 24(8):1260–1270. doi:10.1101/gr.172833.114

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  120. Thomas JH, Schneider S (2011) Coevolution of retroelements and tandem zinc finger genes. Genome Res 21(11):1800–1812. doi:10.1101/gr.121749.111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  121. Schlesinger S, Lee AH, Wang GZ, Green L, Goff SP (2013) Proviral silencing in embryonic cells is regulated by Yin Yang 1. Cell Rep 4(1):50–58. doi:10.1016/j.celrep.2013.06.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  122. Bae EH, Jung YT (2014) Comparison of the effects of retroviral restriction factors involved in resistance to porcine endogenous retrovirus. J Microbiol Biotechnol 24(4):577–583

    Article  CAS  PubMed  Google Scholar 

  123. Nexo BA, Hansen B, Nissen KK, Gundestrup L, Terkelsen T, Villesen P, Bahrami S, Petersen T, Pedersen FS, Laska MJ (2013) Restriction genes for retroviruses influence the risk of multiple sclerosis. PLoS ONE 8(9):e74063. doi:10.1371/journal.pone.0074063

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  124. Yu P, Lubben W, Slomka H, Gebler J, Konert M, Cai C, Neubrandt L, Prazeres da Costa O, Paul S, Dehnert S, Dohne K, Thanisch M, Storsberg S, Wiegand L, Kaufmann A, Nain M, Quintanilla-Martinez L, Bettio S, Schnierle B, Kolesnikova L, Becker S, Schnare M, Bauer S (2012) Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors. Immunity 37(5):867–879. doi:10.1016/j.immuni.2012.07.018

    Article  CAS  PubMed  Google Scholar 

  125. Liberatore RA, Bieniasz PD (2011) Tetherin is a key effector of the antiretroviral activity of type I interferon in vitro and in vivo. Proc Natl Acad Sci USA 108(44):18097–18101. doi:10.1073/pnas.1113694108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  126. Lemaitre C, Harper F, Pierron G, Heidmann T, Dewannieux M (2014) The HERV-K human endogenous retrovirus envelope protein antagonizes Tetherin antiviral activity. J Virol 88(23):13626–13637. doi:10.1128/JVI.02234-14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  127. Goila-Gaur R, Strebel K (2008) HIV-1 Vif, APOBEC, and intrinsic immunity. Retrovirology 5:51. doi:10.1186/1742-4690-5-51

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  128. Holmes RK, Malim MH, Bishop KN (2007) APOBEC-mediated viral restriction: not simply editing? Trends Biochem Sci 32(3):118–128. doi:10.1016/j.tibs.2007.01.004

    Article  CAS  PubMed  Google Scholar 

  129. Santoni FA, Guerra J, Luban J (2012) HERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency. Retrovirology 9:111. doi:10.1186/1742-4690-9-111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  130. Ohnuki M, Tanabe K, Sutou K, Teramoto I, Sawamura Y, Narita M, Nakamura M, Tokunaga Y, Nakamura M, Watanabe A, Yamanaka S, Takahashi K (2014) Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential. Proc Natl Acad Sci USA 111(34):12426–12431. doi:10.1073/pnas.1413299111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  131. Lu X, Sachs F, Ramsay L, Jacques PE, Goke J, Bourque G, Ng HH (2014) The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nat Struct Mol Biol 21(4):423–425. doi:10.1038/nsmb.2799

    Article  CAS  PubMed  Google Scholar 

  132. Andersson AC, Venables PJ, Tonjes RR, Scherer J, Eriksson L, Larsson E (2002) Developmental expression of HERV-R (ERV3) and HERV-K in human tissue. Virology 297(2):220–225

    Article  CAS  PubMed  Google Scholar 

  133. Frendo JL, Olivier D, Cheynet V, Blond JL, Bouton O, Vidaud M, Rabreau M, Evain-Brion D, Mallet F (2003) Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Mol Cell Biol 23(10):3566–3574

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  134. Dunk CE, Gellhaus A, Drewlo S, Baczyk D, Potgens AJ, Winterhager E, Kingdom JC, Lye SJ (2012) The molecular role of connexin 43 in human trophoblast cell fusion. Biol Reprod 86(4):115. doi:10.1095/biolreprod.111.096925

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  135. Ruebner M, Strissel PL, Ekici AB, Stiegler E, Dammer U, Goecke TW, Faschingbauer F, Fahlbusch FB, Beckmann MW, Strick R (2013) Reduced syncytin-1 expression levels in placental syndromes correlates with epigenetic hypermethylation of the ERVW-1 promoter region. PLoS ONE 8(2):e56145. doi:10.1371/journal.pone.0056145

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  136. Seabrook JL, Cantlon JD, Cooney AJ, McWhorter EE, Fromme BA, Bouma GJ, Anthony RV, Winger QA (2013) Role of LIN28A in mouse and human trophoblast cell differentiation. Biol Reprod 89(4):95. doi:10.1095/biolreprod.113.109868

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  137. Rote NS, Chakrabarti S, Stetzer BP (2004) The role of human endogenous retroviruses in trophoblast differentiation and placental development. Placenta 25(8–9):673–683. doi:10.1016/j.placenta.2004.02.008

    Article  CAS  PubMed  Google Scholar 

  138. Lokossou AG, Toudic C, Barbeau B (2014) Implication of human endogenous retrovirus envelope proteins in placental functions. Viruses 6(11):4609–4627. doi:10.3390/v6114609

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  139. Esnault C, Cornelis G, Heidmann O, Heidmann T (2013) Differential evolutionary fate of an ancestral primate endogenous retrovirus envelope gene, the EnvV syncytin, captured for a function in placentation. PLoS Genet 9(3):e1003400. doi:10.1371/journal.pgen.1003400

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  140. Pi W, Zhu X, Wu M, Wang Y, Fulzele S, Eroglu A, Ling J, Tuan D (2010) Long-range function of an intergenic retrotransposon. Proc Natl Acad Sci USA 107(29):12992–12997. doi:10.1073/pnas.1004139107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  141. Long Q, Bengra C, Li C, Kutlar F, Tuan D (1998) A long terminal repeat of the human endogenous retrovirus ERV-9 is located in the 5′ boundary area of the human beta-globin locus control region. Genomics 54(3):542–555. doi:10.1006/geno.1998.5608

    Article  CAS  PubMed  Google Scholar 

  142. Ling J, Pi W, Bollag R, Zeng S, Keskintepe M, Saliman H, Krantz S, Whitney B, 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(5):2410–2423

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  143. Dunn CA, van de Lagemaat LN, Baillie GJ, Mager DL (2005) Endogenous retrovirus long terminal repeats as ready-to-use mobile promoters: the case of primate beta3GAL-T5. Gene 364:2–12. doi:10.1016/j.gene.2005.05.045

    Article  CAS  PubMed  Google Scholar 

  144. Romanish MT, Lock WM, van de Lagemaat LN, Dunn CA, Mager DL (2007) Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution. PLoS Genet 3(1):e10. doi:10.1371/journal.pgen.0030010

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  145. Landry JR, Rouhi A, Medstrand P, Mager DL (2002) The Opitz syndrome gene Mid1 is transcribed from a human endogenous retroviral promoter. Mol Biol Evol 19(11):1934–1942

    Article  CAS  PubMed  Google Scholar 

  146. Medstrand P, Landry JR, Mager DL (2001) Long terminal repeats are used as alternative promoters for the endothelin B receptor and apolipoprotein C-I genes in humans. J Biol Chem 276(3):1896–1903. doi:10.1074/jbc.M006557200

    Article  CAS  PubMed  Google Scholar 

  147. Bieche I, Laurent A, Laurendeau I, Duret L, Giovangrandi Y, Frendo JL, Olivi M, Fausser JL, Evain-Brion D, Vidaud M (2003) Placenta-specific INSL4 expression is mediated by a human endogenous retrovirus element. Biol Reprod 68(4):1422–1429. doi:10.1095/biolreprod.102.010322

    Article  CAS  PubMed  Google Scholar 

  148. Carlton VE, Harris BZ, Puffenberger EG, Batta AK, Knisely AS, Robinson DL, Strauss KA, Shneider BL, Lim WA, Salen G, Morton DH, Bull LN (2003) Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet 34(1):91–96. doi:10.1038/ng1147

    Article  CAS  PubMed  Google Scholar 

  149. Mason MJ, Speake C, Gersuk VH, Nguyen QA, O’Brien KK, Odegard JM, Buckner JH, Greenbaum CJ, Chaussabel D, Nepom GT (2014) Low HERV-K(C4) copy number is associated with type 1 diabetes. Diabetes 63(5):1789–1795. doi:10.2337/db13-1382

    Article  CAS  PubMed  Google Scholar 

  150. Young GR, Stoye JP, Kassiotis G (2013) Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis. BioEssays 35(9):794–803. doi:10.1002/bies.201300049

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  151. Tugnet N, Rylance P, Roden D, Trela M, Nelson P (2013) Human endogenous retroviruses (HERVs) and autoimmune rheumatic disease: is there a link? Open Rheumatol J 7:13–21. doi:10.2174/1874312901307010013

    PubMed Central  CAS  PubMed  Google Scholar 

  152. Cusick MF, Libbey JE, Fujinami RS (2013) Multiple sclerosis: autoimmunity and viruses. Curr Opin Rheumatol 25(4):496–501. doi:10.1097/BOR.0b013e328362004d

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  153. Ehlhardt S, Seifert M, Schneider J, Ojak A, Zang KD, Mehraein Y (2006) Human endogenous retrovirus HERV-K(HML-2) Rec expression and transcriptional activities in normal and rheumatoid arthritis synovia. J Rheumatol 33(1):16–23

    CAS  PubMed  Google Scholar 

  154. Wu Z, Mei X, Zhao D, Sun Y, Song J, Pan W, Shi W (2015) DNA methylation modulates HERV-E expression in CD4+ T cells from systemic lupus erythematosus patients. J Dermatol Sci 77(2):110–116. doi:10.1016/j.jdermsci.2014.12.004

    Article  CAS  PubMed  Google Scholar 

  155. Nelson P, Rylance P, Roden D, Trela M, Tugnet N (2014) Viruses as potential pathogenic agents in systemic lupus erythematosus. Lupus 23(6):596–605. doi:10.1177/0961203314531637

    Article  CAS  PubMed  Google Scholar 

  156. Nakkuntod J, Sukkapan P, Avihingsanon Y, Mutirangura A, Hirankarn N (2013) DNA methylation of human endogenous retrovirus in systemic lupus erythematosus. J Hum Genet 58(5):241–249. doi:10.1038/jhg.2013.6

    Article  CAS  PubMed  Google Scholar 

  157. Shi L, Zhang Z, Yu AM, Wang W, Wei Z, Akhter E, Maurer K, Costa Reis P, Song L, Petri M, Sullivan KE (2014) The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. PLoS ONE 9(5):e93846. doi:10.1371/journal.pone.0093846

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  158. Nelson PN, Roden D, Nevill A, Freimanis GL, Trela M, Ejtehadi HD, Bowman S, Axford J, Veitch AM, Tugnet N, Rylance PB (2014) Rheumatoid arthritis is associated with IgG antibodies to human endogenous retrovirus gag matrix: a potential pathogenic mechanism of disease? J Rheumatol 41(10):1952–1960. doi:10.3899/jrheum.130502

    Article  CAS  PubMed  Google Scholar 

  159. Bendiksen S, Martinez-Zubiavrra I, Tummler C, Knutsen G, Elvenes J, Olsen E, Olsen R, Moens U (2014) Human endogenous retrovirus W activity in cartilage of osteoarthritis patients. Biomed Res Int 2014:698609. doi:10.1155/2014/698609

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  160. Garcia-Montojo M, Varade J, Villafuertes E, de La Hera B, Hoyas-Fernandez J, Dominguez-Mozo MI, Rodriguez-Rodriguez L, Tornero-Esteban P, Arias-Leal A, Leon L, Lamas JR, Alvarez-Lafuente R, Urcelay E, Fernandez-Gutierrez B (2013) Expression of human endogenous retrovirus HERV-K18 is associated with clinical severity in osteoarthritis patients. Scand J Rheumatol 42(6):498–504. doi:10.3109/03009742.2013.779021

    Article  CAS  PubMed  Google Scholar 

  161. Manghera M, Douville RN (2013) Endogenous retrovirus-K promoter: a landing strip for inflammatory transcription factors? Retrovirology 10:16. doi:10.1186/1742-4690-10-16

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  162. de Sousa Nogueira MA, Biancardi Gavioli CF, Pereira NZ, de Carvalho GC, Domingues R, Aoki V, Sato MN (2015) Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus. Arch Dermatol Res 307(3):259–264. doi:10.1007/s00403-014-1524-0

    Article  CAS  Google Scholar 

  163. Gupta R, Michaud HA, Zeng X, Debbaneh M, Arron ST, Jones RB, Ormsby CE, Nixon DF, Liao W (2014) Diminished humoral responses against and reduced gene expression levels of human endogenous retrovirus-K (HERV-K) in psoriasis. J Transl Med 12:256. doi:10.1186/s12967-014-0256-4

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  164. Fowler BJ, Gelfand BD, Kim Y, Kerur N, Tarallo V, Hirano Y, Amarnath S, Fowler DH, Radwan M, Young MT, Pittman K, Kubes P, Agarwal HK, Parang K, Hinton DR, Bastos-Carvalho A, Li S, Yasuma T, Mizutani T, Yasuma R, Wright C, Ambati J (2014) Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity. Science 346(6212):1000–1003. doi:10.1126/science.1261754

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  165. Manghera M, Ferguson J, Douville R (2015) ERVK polyprotein processing and reverse transcriptase expression in human cell line models of neurological disease. Viruses 7(1):320–332. doi:10.3390/v7010320

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  166. Christensen T (2010) HERVs in neuropathogenesis. J Neuroimmune Pharmacol 5(3):326–335. doi:10.1007/s11481-010-9214-y

    Article  PubMed  Google Scholar 

  167. Alfahad T, Nath A (2013) Retroviruses and amyotrophic lateral sclerosis. Antiviral Res 99(2):180–187. doi:10.1016/j.antiviral.2013.05.006

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  168. Libbey JE, Cusick MF, Fujinami RS (2014) Role of pathogens in multiple sclerosis. Int Rev Immunol 33(4):266–283. doi:10.3109/08830185.2013.823422

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  169. Emmer A, Staege MS, Kornhuber ME (2014) The retrovirus/superantigen hypothesis of multiple sclerosis. Cell Mol Neurobiol 34(8):1087–1096. doi:10.1007/s10571-014-0100-7

    Article  CAS  PubMed  Google Scholar 

  170. de la Hera B, Varade J, Garcia-Montojo M, Alcina A, Fedetz M, Alloza I, Astobiza I, Leyva L, Fernandez O, Izquierdo G, Antiguedad A, Arroyo R, Alvarez-Lafuente R, Vandenbroeck K, Matesanz F, Urcelay E (2014) Human endogenous retrovirus HERV-Fc1 association with multiple sclerosis susceptibility: a meta-analysis. PLoS ONE 9(3):e90182. doi:10.1371/journal.pone.0090182

    Article  PubMed Central  PubMed  Google Scholar 

  171. de la Hera B, Varade J, Garcia-Montojo M, Lamas JR, de la Encarnacion A, Arroyo R, Fernandez-Gutierrez B, Alvarez-Lafuente R, Urcelay E (2013) Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis. PLoS ONE 8(4):e62090. doi:10.1371/journal.pone.0062090

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  172. Garcia-Montojo M, de la Hera B, Varade J, de la Encarnacion A, Camacho I, Dominguez-Mozo M, Arias-Leal A, Garcia-Martinez A, Casanova I, Izquierdo G, Lucas M, Fedetz M, Alcina A, Arroyo R, Matesanz F, Urcelay E, Alvarez-Lafuente R (2014) HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV. Retrovirology 11:2. doi:10.1186/1742-4690-11-2

    Article  PubMed Central  PubMed  Google Scholar 

  173. Perron H, Dougier-Reynaud HL, Lomparski C, Popa I, Firouzi R, Bertrand JB, Marusic S, Portoukalian J, Jouvin-Marche E, Villiers CL, Touraine JL, Marche PN (2013) Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice. PLoS ONE 8(12):e80128. doi:10.1371/journal.pone.0080128

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  174. Mameli G, Madeddu G, Mei A, Uleri E, Poddighe L, Delogu LG, Maida I, Babudieri S, Serra C, Manetti R, Mura MS, Dolei A (2013) Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the missing link with multiple sclerosis? PLoS ONE 8(11):e78474. doi:10.1371/journal.pone.0078474

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  175. Arru G, Leoni S, Pugliatti M, Mei A, Serra C, Delogu LG, Manetti R, Dolei A, Sotgiu S, Mameli G (2014) Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: a longitudinal cohort study. Mult Scler 20(2):174–182. doi:10.1177/1352458513494957

    Article  PubMed  CAS  Google Scholar 

  176. Diem O, Schaffner M, Seifarth W, Leib-Mosch C (2012) Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells. PLoS ONE 7(1):e30054. doi:10.1371/journal.pone.0030054

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  177. Liu C, Chen Y, Li S, Yu H, Zeng J, Wang X, Zhu F (2013) Activation of elements in HERV-W family by caffeine and aspirin. Virus Genes 47(2):219–227. doi:10.1007/s11262-013-0939-6

    Article  CAS  PubMed  Google Scholar 

  178. Nissen KK, Laska MJ, Hansen B, Terkelsen T, Villesen P, Bahrami S, Petersen T, Pedersen FS, Nexo BA (2013) Endogenous retroviruses and multiple sclerosis-new pieces to the puzzle. BMC Neurol 13:111. doi:10.1186/1471-2377-13-111

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  179. Hon GM, Erasmus RT, Matsha T (2013) Multiple sclerosis-associated retrovirus and related human endogenous retrovirus-W in patients with multiple sclerosis: a literature review. J Neuroimmunol 263(1–2):8–12. doi:10.1016/j.jneuroim.2013.08.005

    Article  CAS  PubMed  Google Scholar 

  180. Gold J, Goldacre R, Maruszak H, Giovannoni G, Yeates D, Goldacre M (2015) HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database study. J Neurol Neurosurg Psychiatry 86(1):9–12. doi:10.1136/jnnp-2014-307932

    Article  PubMed Central  PubMed  Google Scholar 

  181. Li S, Liu ZC, Yin SJ, Chen YT, Yu HL, Zeng J, Zhang Q, Zhu F (2013) Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB. Neuroscience 247:164–174. doi:10.1016/j.neuroscience.2013.05.033

    Article  CAS  PubMed  Google Scholar 

  182. Perron H, Hamdani N, Faucard R, Lajnef M, Jamain S, Daban-Huard C, Sarrazin S, LeGuen E, Houenou J, Delavest M, Moins-Teisserenc H, Bengoufa D, Yolken R, Madeira A, Garcia-Montojo M, Gehin N, Burgelin I, Ollagnier G, Bernard C, Dumaine A, Henrion A, Gombert A, Le Dudal K, Charron D, Krishnamoorthy R, Tamouza R, Leboyer M (2012) Molecular characteristics of human endogenous retrovirus type-W in schizophrenia and bipolar disorder. Transl Psychiatry 2:e201. doi:10.1038/tp.2012.125

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  183. Nyegaard M, Demontis D, Thestrup BB, Hedemand A, Sorensen KM, Hansen T, Werge T, Hougaard DM, Yolken RH, Mortensen PB, Mors O, Borglum AD (2012) No association of polymorphisms in human endogenous retrovirus K18 and CD48 with schizophrenia. Psychiatr Genet 22(3):146–148. doi:10.1097/YPG.0b013e328353953c

    Article  PubMed  Google Scholar 

  184. Shuvarikov A, Campbell IM, Dittwald P, Neill NJ, Bialer MG, Moore C, Wheeler PG, Wallace SE, Hannibal MC, Murray MF, Giovanni MA, Terespolsky D, Sodhi S, Cassina M, Viskochil D, Moghaddam B, Herman K, Brown CW, Beck CR, Gambin A, Cheung SW, Patel A, Lamb AN, Shaffer LG, Ellison JW, Ravnan JB, Stankiewicz P, Rosenfeld JA (2013) Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays. Hum Mutat 34(10):1415–1423. doi:10.1002/humu.22384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Contreras-Galindo R, Lopez P, Velez R, Yamamura Y (2007) HIV-1 infection increases the expression of human endogenous retroviruses type K (HERV-K) in vitro. AIDS Res Hum Retroviruses 23(1):116–122. doi:10.1089/aid.2006.0117

    Article  CAS  PubMed  Google Scholar 

  186. Contreras-Galindo R, Gonzalez M, Almodovar-Camacho S, Gonzalez-Ramirez S, Lorenzo E, Yamamura Y (2006) A new real-time-RT-PCR for quantitation of human endogenous retroviruses type K (HERV-K) RNA load in plasma samples: increased HERV-K RNA titers in HIV-1 patients with HAART non-suppressive regimens. J Virol Methods 136(1–2):51–57. doi:10.1016/j.jviromet.2006.03.029

    Article  CAS  PubMed  Google Scholar 

  187. Bhardwaj N, Maldarelli F, Mellors J, Coffin JM (2014) HIV-1 infection leads to increased transcription of human endogenous retrovirus HERV-K (HML-2) proviruses in vivo but not to increased virion production. J Virol 88(19):11108–11120. doi:10.1128/JVI.01623-14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  188. Li L, Deng X, Linsuwanon P, Bangsberg D, Bwana MB, Hunt P, Martin JN, Deeks SG, Delwart E (2013) AIDS alters the commensal plasma virome. J Virol 87(19):10912–10915. doi:10.1128/JVI.01839-13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  189. Esqueda D, Xu F, Moore Y, Yang Z, Huang G, Lennon PA, Hu PC, Dong J (2013) Lack of correlation between HERV-K expression and HIV-1 viral load in plasma specimens. Ann Clin Lab Sci 43(2):122–125

    CAS  PubMed  Google Scholar 

  190. Michaud HA, de Mulder M, SenGupta D, Deeks SG, Martin JN, Pilcher CD, Hecht FM, Sacha JB, Nixon DF (2014) Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection. Retrovirology 11:10. doi:10.1186/1742-4690-11-10

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  191. Jones RB, Garrison KE, Mujib S, Mihajlovic V, Aidarus N, Hunter DV, Martin E, John VM, Zhan W, Faruk NF, Gyenes G, Sheppard NC, Priumboom-Brees IM, Goodwin DA, Chen L, Rieger M, Muscat-King S, Loudon PT, Stanley C, Holditch SJ, Wong JC, Clayton K, Duan E, Song H, Xu Y, SenGupta D, Tandon R, Sacha JB, Brockman MA, Benko E, Kovacs C, Nixon DF, Ostrowski MA (2012) HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates. J Clin Investig 122(12):4473–4489. doi:10.1172/JCI64560

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  192. Jones RB, Song H, Xu Y, Garrison KE, Buzdin AA, Anwar N, Hunter DV, Mujib S, Mihajlovic V, Martin E, Lee E, Kuciak M, Raposo RA, Bozorgzad A, Meiklejohn DA, Ndhlovu LC, Nixon DF, Ostrowski MA (2013) LINE-1 retrotransposable element DNA accumulates in HIV-1-infected cells. J Virol 87(24):13307–13320. doi:10.1128/JVI.02257-13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  193. Gonzalez-Hernandez MJ, Cavalcoli JD, Sartor MA, Contreras-Galindo R, Meng F, Dai M, Dube D, Saha AK, Gitlin SD, Omenn GS, Kaplan MH, Markovitz DM (2014) Regulation of the human endogenous retrovirus K (HML-2) transcriptome by the HIV-1 Tat protein. J Virol 88(16):8924–8935. doi:10.1128/JVI.00556-14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  194. Uleri E, Mei A, Mameli G, Poddighe L, Serra C, Dolei A (2014) HIV Tat acts on endogenous retroviruses of the W family and this occurs via Toll-like receptor 4: inference for neuroAIDS. AIDS 28(18):2659–2670. doi:10.1097/QAD.0000000000000477

    Article  CAS  PubMed  Google Scholar 

  195. Spencer TE, Mura M, Gray CA, Griebel PJ, Palmarini M (2003) Receptor usage and fetal expression of ovine endogenous betaretroviruses: implications for coevolution of endogenous and exogenous retroviruses. J Virol 77(1):749–753

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  196. Ponferrada VG, Mauck BS, Wooley DP (2003) The envelope glycoprotein of human endogenous retrovirus HERV-W induces cellular resistance to spleen necrosis virus. Arch Virol 148(4):659–675. doi:10.1007/s00705-002-0960-x

    Article  CAS  PubMed  Google Scholar 

  197. Best S, Le Tissier PR, Stoye JP (1997) Endogenous retroviruses and the evolution of resistance to retroviral infection. Trends Microbiol 5(8):313–318. doi:10.1016/S0966-842X(97)01086-X

    Article  CAS  PubMed  Google Scholar 

  198. Fujino K, Horie M, Honda T, Merriman DK, Tomonaga K (2014) Inhibition of Borna disease virus replication by an endogenous bornavirus-like element in the ground squirrel genome. Proc Natl Acad Sci USA 111(36):13175–13180. doi:10.1073/pnas.1407046111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  199. Malfavon-Borja R, Feschotte C (2015) Fighting fire with fire: endogenous retrovirus envelopes as restriction factors. J Virol. doi:10.1128/JVI.03653-14

    PubMed  PubMed Central  Google Scholar 

  200. Crosslin DR, Carrell DS, Burt A, Kim DS, Underwood JG, Hanna DS, Comstock BA, Baldwin E, de Andrade M, Kullo IJ, Tromp G, Kuivaniemi H, Borthwick KM, McCarty CA, Peissig PL, Doheny KF, Pugh E, Kho A, Pacheco J, Hayes MG, Ritchie MD, Verma SS, Armstrong G, Stallings S, Denny JC, Carroll RJ, Crawford DC, Crane PK, Mukherjee S, Bottinger E, Li R, Keating B, Mirel DB, Carlson CS, Harley JB, Larson EB, Jarvik GP (2015) Genetic variation in the HLA region is associated with susceptibility to herpes zoster. Genes Immun 16(1):1–7. doi:10.1038/gene.2014.51

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  201. Lee E, Iskow R, Yang L, Gokcumen O, Haseley P, Luquette LJ 3rd, Lohr JG, Harris CC, Ding L, Wilson RK, Wheeler DA, Gibbs RA, Kucherlapati R, Lee C, Kharchenko PV, Park PJ, Cancer Genome Atlas Research Network (2012) Landscape of somatic retrotransposition in human cancers. Science 337(6097):967–971. doi:10.1126/science.1222077

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  202. Gualtieri A, Andreola F, Sciamanna I, Sinibaldi-Vallebona P, Serafino A, Spadafora C (2013) Increased expression and copy number amplification of LINE-1 and SINE B1 retrotransposable elements in murine mammary carcinoma progression. Oncotarget 4(11):1882–1893

    Article  PubMed Central  PubMed  Google Scholar 

  203. Oricchio E, Sciamanna I, Beraldi R, Tolstonog GV, Schumann GG, Spadafora C (2007) Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression. Oncogene 26(29):4226–4233. doi:10.1038/sj.onc.1210214

    Article  CAS  PubMed  Google Scholar 

  204. Muster T, Waltenberger A, Grassauer A, Hirschl S, Caucig P, Romirer I, Fodinger D, Seppele H, Schanab O, Magin-Lachmann C, Lower R, Jansen B, Pehamberger H, Wolff K (2003) An endogenous retrovirus derived from human melanoma cells. Cancer Res 63(24):8735–8741

    CAS  PubMed  Google Scholar 

  205. Schmitt K, Reichrath J, Roesch A, Meese E, Mayer J (2013) Transcriptional profiling of human endogenous retrovirus group HERV-K(HML-2) loci in melanoma. Genome Biol Evol 5(2):307–328. doi:10.1093/gbe/evt010

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  206. Katoh I, Mirova A, Kurata S, Murakami Y, Horikawa K, Nakakuki N, Sakai T, Hashimoto K, Maruyama A, Yonaga T, Fukunishi N, Moriishi K, Hirai H (2011) Activation of the long terminal repeat of human endogenous retrovirus K by melanoma-specific transcription factor MITF-M. Neoplasia 13(11):1081–1092

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  207. Wang-Johanning F, Li M, Esteva FJ, Hess KR, Yin B, Rycaj K, Plummer JB, Garza JG, Ambs S, Johanning GL (2014) Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early-stage breast cancer. Int J Cancer 134(3):587–595. doi:10.1002/ijc.28389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  208. Wallace TA, Downey RF, Seufert CJ, Schetter A, Dorsey TH, Johnson CA, Goldman R, Loffredo CA, Yan P, Sullivan FJ, Giles FJ, Wang-Johanning F, Ambs S, Glynn SA (2014) Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and smokers. Carcinogenesis 35(9):2074–2083. doi:10.1093/carcin/bgu114

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  209. Reis BS, Jungbluth AA, Frosina D, Holz M, Ritter E, Nakayama E, Ishida T, Obata Y, Carver B, Scher H, Scardino PT, Slovin S, Subudhi SK, Reuter VE, Savage C, Allison JP, Melamed J, Jager E, Ritter G, Old LJ, Gnjatic S (2013) Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein. Clin Cancer Res 19(22):6112–6125. doi:10.1158/1078-0432.CCR-12-3580

    Article  CAS  PubMed  Google Scholar 

  210. Takahashi Y, Harashima N, Kajigaya S, Yokoyama H, Cherkasova E, McCoy JP, Hanada K, Mena O, Kurlander R, Tawab A, Srinivasan R, Lundqvist A, Malinzak E, Geller N, Lerman MI, Childs RW (2008) Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells. J Clin Investig 118(3):1099–1109. doi:10.1172/JCI34409

    PubMed Central  CAS  PubMed  Google Scholar 

  211. Fischer S, Echeverria N, Moratorio G, Landoni AI, Dighiero G, Cristina J, Oppezzo P, Moreno P (2014) Human endogenous retrovirus np9 gene is over expressed in chronic lymphocytic leukemia patients. Leuk Res Rep 3(2):70–72. doi:10.1016/j.lrr.2014.06.005

    PubMed Central  PubMed  Google Scholar 

  212. Chen T, Meng Z, Gan Y, Wang X, Xu F, Gu Y, Xu X, Tang J, Zhou H, Zhang X, Gan X, Van Ness C, Xu G, Huang L, Zhang X, Fang Y, Wu J, Zheng S, Jin J, Huang W, Xu R (2013) The viral oncogene Np9 acts as a critical molecular switch for co-activating beta-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells. Leukemia 27(7):1469–1478. doi:10.1038/leu.2013.8

    Article  CAS  PubMed  Google Scholar 

  213. Lavialle C, Cornelis G, Dupressoir A, Esnault C, Heidmann O, Vernochet C, Heidmann T (2013) Paleovirology of ‘syncytins’, retroviral env genes exapted for a role in placentation. Philos Trans R Soc Lond B Biol Sci 368(1626):20120507. doi:10.1098/rstb.2012.0507

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  214. Mangeney M, Heidmann T (1998) Tumor cells expressing a retroviral envelope escape immune rejection in vivo. Proc Natl Acad Sci USA 95(25):14920–14925

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  215. Pothlichet J, Heidmann T, Mangeney M (2006) A recombinant endogenous retrovirus amplified in a mouse neuroblastoma is involved in tumor growth in vivo. Int J Cancer 119(4):815–822. doi:10.1002/ijc.21935

    Article  CAS  PubMed  Google Scholar 

  216. Mangeney M, Pothlichet J, Renard M, Ducos B, Heidmann T (2005) Endogenous retrovirus expression is required for murine melanoma tumor growth in vivo. Cancer Res 65(7):2588–2591. doi:10.1158/0008-5472.CAN-04-4231

    Article  CAS  PubMed  Google Scholar 

  217. Naito T, Ogasawara H, Kaneko H, Hishikawa T, Sekigawa I, Hashimoto H, Maruyama N (2003) Immune abnormalities induced by human endogenous retroviral peptides: with reference to the pathogenesis of systemic lupus erythematosus. J Clin Immunol 23(5):371–376

    Article  CAS  PubMed  Google Scholar 

  218. Mangeney M, de Parseval N, Thomas G, Heidmann T (2001) The full-length envelope of an HERV-H human endogenous retrovirus has immunosuppressive properties. J Gen Virol 82(Pt 10):2515–2518

    Article  CAS  PubMed  Google Scholar 

  219. Rhyu DW, Kang YJ, Ock MS, Eo JW, Choi YH, Kim WJ, Leem SH, Yi JM, Kim HS, Cha HJ (2014) Expression of human endogenous retrovirus env genes in the blood of breast cancer patients. Int J Mol Sci 15(6):9173–9183. doi:10.3390/ijms15069173

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  220. Strissel PL, Ruebner M, Thiel F, Wachter D, Ekici AB, Wolf F, Thieme F, Ruprecht K, Beckmann MW, Strick R (2012) Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: emergence of new molecular targets. Oncotarget 3(10):1204–1219

    Article  PubMed Central  PubMed  Google Scholar 

  221. Lamprecht B, Walter K, Kreher S, Kumar R, Hummel M, Lenze D, Kochert K, Bouhlel MA, Richter J, Soler E, Stadhouders R, Johrens K, Wurster KD, Callen DF, Harte MF, Giefing M, Barlow R, Stein H, Anagnostopoulos I, Janz M, Cockerill PN, Siebert R, Dorken B, Bonifer C, Mathas S (2010) Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nat Med 16(5):571–579. doi:10.1038/nm.2129

    Article  CAS  PubMed  Google Scholar 

  222. Hayes M, Whitesell M, Brown MA (2013) Pathological and evolutionary implications of retroviruses as mobile genetic elements. Genes 4(4):573–582. doi:10.3390/genes4040573

    Article  PubMed Central  PubMed  Google Scholar 

  223. Subramanian RP, Wildschutte JH, Russo C, Coffin JM (2011) Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses. Retrovirology 8:90. doi:10.1186/1742-4690-8-90

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  224. Lee A, Huntley D, Aiewsakun P, Kanda RK, Lynn C, Tristem M (2014) Novel Denisovan and Neanderthal retroviruses. J Virol 88(21):12907–12909. doi:10.1128/JVI.01825-14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  225. Beaune J, Nony P, Chassignolle J, Loire R, Gros P, Delaye J (1989) Aortic insufficiency caused by dystrophic aneurysm of the ascending aorta: study of development in 95 cases. Value of cutaneous biopsy in the etiologic diagnosis. Arch Mal Coeur Vaiss 82(8):1389–1396

    CAS  PubMed  Google Scholar 

  226. Anisimova M, Liberles DA (2007) The quest for natural selection in the age of comparative genomics. Heredity 99(6):567–579. doi:10.1038/sj.hdy.6801052

    Article  CAS  PubMed  Google Scholar 

  227. Kao TH, Liao HF, Wolf D, Tai KY, Chuang CY, Lee HS, Kuo HC, Hata K, Zhang X, Cheng X, Goff SP, Ooi SK, Bestor TH, Lin SP (2014) Ectopic DNMT3L triggers assembly of a repressive complex for retroviral silencing in somatic cells. J Virol 88(18):10680–10695. doi:10.1128/JVI.01176-14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  228. Kuzmin D, Gogvadze E, Kholodenko R, Grzela DP, Mityaev M, Vinogradova T, Kopantzev E, Malakhova G, Suntsova M, Sokov D, Ivics Z, Buzdin A (2010) Novel strong tissue specific promoter for gene expression in human germ cells. BMC Biotechnol 10:58. doi:10.1186/1472-6750-10-58

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  229. Fuchs NV, Kraft M, Tondera C, Hanschmann KM, Lower J, Lower R (2011) Expression of the human endogenous retrovirus (HERV) group HML-2/HERV-K does not depend on canonical promoter elements but is regulated by transcription factors Sp1 and Sp3. J Virol 85(7):3436–3448. doi:10.1128/JVI.02539-10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  230. Hughes JF, Coffin JM (2001) Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet 29(4):487–489. doi:10.1038/ng775

    Article  CAS  PubMed  Google Scholar 

  231. Paces J, Pavlicek A, Zika R, Kapitonov VV, Jurka J, Paces V (2004) HERVd: the human endogenous retroviruses database: update. Nucleic Acids Res 32(Database issue):D50. doi:10.1093/nar/gkh075

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  232. Villesen P, Aagaard L, Wiuf C, Pedersen FS (2004) Identification of endogenous retroviral reading frames in the human genome. Retrovirology 1:32. doi:10.1186/1742-4690-1-32

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  233. Wang J, Song L, Grover D, Azrak S, Batzer MA, Liang P (2006) dbRIP: a highly integrated database of retrotransposon insertion polymorphisms in humans. Hum Mutat 27(4):323–329. doi:10.1002/humu.20307

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  234. Mills RE, Bennett EA, Iskow RC, Luttig CT, Tsui C, Pittard WS, Devine SE (2006) Recently mobilized transposons in the human and chimpanzee genomes. Am J Hum Genet 78(4):671–679. doi:10.1086/501028

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  235. Hernandez-Pinzon I, de Jesus E, Santiago N, Casacuberta JM (2009) The frequent transcriptional readthrough of the tobacco Tnt1 retrotransposon and its possible implications for the control of resistance genes. J Mol Evol 68(3):269–278. doi:10.1007/s00239-009-9204-y

    Article  CAS  PubMed  Google Scholar 

  236. Piriyapongsa J, Jordan IK (2007) A family of human microRNA genes from miniature inverted-repeat transposable elements. PLoS ONE 2(2):e203. doi:10.1371/journal.pone.0000203

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  237. Levy A, Sela N, Ast G (2008) TranspoGene and microTranspoGene: transposed elements influence on the transcriptome of seven vertebrates and invertebrates. Nucleic acids research 36(Database issue):D47–D52. doi:10.1093/nar/gkm949

    PubMed Central  CAS  PubMed  Google Scholar 

  238. Kim TH, Jeon YJ, Kim WY, Kim HS (2005) HESAS: HERVs expression and structure analysis system. Bioinformatics 21(8):1699–1700. doi:10.1093/bioinformatics/bti194

    Article  CAS  PubMed  Google Scholar 

  239. Sperber GO, Airola T, Jern P, Blomberg J (2007) Automated recognition of retroviral sequences in genomic data—RetroTector. Nucleic Acids Res 35(15):4964–4976. doi:10.1093/nar/gkm515

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  240. Zhavoronkov A, Cantor CR (2011) Methods for structuring scientific knowledge from many areas related to aging research. PLoS ONE 6(7):e22597. doi:10.1371/journal.pone.0022597

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Pathway Pharmaceuticals Research Initiative (Hong-Kong) and by the Program of the Presidium of the Russian Academy of Sciences “Dynamics and Conservation of Genomes”. The authors thank “UMA Foundation” for their help in preparation of the manuscript.

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Authors and Affiliations

  1. Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia

    Maria Suntsova, Andrew Garazha, Alena Ivanova & Anton Buzdin

  2. Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, 117198, Russia

    Maria Suntsova & Andrew Garazha

  3. Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR

    Alena Ivanova, Dmitry Kaminsky, Alex Zhavoronkov & Anton Buzdin

  4. Department of Translational and Regenerative Medicine, Moscow Institute of Physics and Technology, 9 Institutskiy per., Dolgoprudny, Moscow, 141700, Russia

    Alex Zhavoronkov

  5. National Research Centre “Kurchatov Institute”, Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies, 1, Akademika Kurchatova sq., Moscow, 123182, Russia

    Anton Buzdin

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  1. Maria Suntsova
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Suntsova, M., Garazha, A., Ivanova, A. et al. Molecular functions of human endogenous retroviruses in health and disease. Cell. Mol. Life Sci. 72, 3653–3675 (2015). https://doi.org/10.1007/s00018-015-1947-6

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  • DOI: https://doi.org/10.1007/s00018-015-1947-6

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