Skip to main content

Advertisement

SpringerLink
Log in

Evidence for the persistence of an active endogenous retrovirus (ERVE) in humans

  • Published:
Genetica Aims and scope Submit manuscript

Abstract

Transposable elements (TEs) account for nearly half (44 %) of the human genome. However, their overall activity has been steadily declining over the past 35–50 million years, so that <0.05 % of TEs are presumably still “alive” (potentially transposable) in human populations. All the active elements are retrotransposons, either autonomous (LINE-1 and possibly the endogenous retrovirus ERVK), or non-autonomous (Alu and SVA, whose transposition is dependent on the LINE-1 enzymatic machinery). Here we show that a lineage of the endogenous retrovirus ERVE was recently engaged in ectopic recombination events and may have at least one potentially fully functional representative, initially reported as a novel retrovirus isolated from blood cells of a Chinese patient with chronic myeloid leukemia, which bears signals of positive selection on its envelope region. Altogether, there is strong evidence that ERVE should be included in the short list of potentially active TEs, and we give clues on how to identify human specific insertions of this element that are likely to be segregating in some of our populations.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Arnaud F, Caporale M, Varela M, Biek R, Chessa B et al (2007) A paradigm for virus–host coevolution: sequential counter-adaptations between endogenous and exogenous retroviruses. PLoS Pathog 3:e170

    Article  PubMed  PubMed Central  Google Scholar 

  • Balada E, Ordi-Ros J, Vilardell-Tarrés M (2009) Molecular mechanisms mediated by human endogenous retroviruses (HERVs) in autoimmunity. Rev Med Virol 19:273–286

    Article  PubMed  CAS  Google Scholar 

  • 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  CAS  PubMed Central  Google Scholar 

  • Bannert N, Kurth R (2006) The evolutionary dynamics of human endogenous retroviral families. Annu Rev Genomics Hum Genet 7:149–173

    Article  PubMed  CAS  Google Scholar 

  • Bartolome C, Bello X, Maside X (2009) Widespread evidence for horizontal transfer of transposable elements across Drosophila genomes. Genome Biol 10:R22

    Article  PubMed  PubMed Central  Google Scholar 

  • Belshaw R, Katzourakis A, Paces J, Burt A, Tristem M (2005) High copy number in human endogenous retrovirus families is associated with copying mechanisms in addition to reinfection. Mol Biol Evol 22:814–817

    Article  PubMed  CAS  Google Scholar 

  • Berglund J, Pollard KS, Webster MT (2009) Hotspots of biased nucleotide substitutions in human genes. PLoS Biol 7:e26

    Article  PubMed  Google Scholar 

  • Best S, Le Tissier PR, Stoye JP (1997) Endogenous retroviruses and the evolution of resistance to retroviral infection. Trends Microbiol 5:313–318

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Cann HM, de Toma C, Cazes L, Legrand M-F, Morel V et al (2002) A human genome diversity cell line panel. Science 296:261

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Cordaux R, Batzer MA (2009) The impact of retrotransposons on human genome evolution. Nat Rev Genet 10:691–703

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • de Parseval N, Heidmann T (2005) Human endogenous retroviruses: from infectious elements to human genes. Cytogenet Genome Res 110:318–332

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Dolei A (2006) Endogenous retroviruses and human disease. Expert Rev Clin Immunol 2:149–167

    Article  PubMed  CAS  Google Scholar 

  • Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Feschotte C, Gilbert C (2012) Endogenous viruses: insights into viral evolution and impact on host biology. Nat Rev Genet 13:283–296

    Article  PubMed  CAS  Google Scholar 

  • Gifford R, Tristem M (2003) The evolution, distribution and diversity of endogenous retroviruses. Virus Genes 26:291–315

    Article  PubMed  CAS  Google Scholar 

  • Hall TA (1999) BIOEDIT: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98

    CAS  Google Scholar 

  • Hughes JF, Coffin JM (2005) Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome. Genetics 171:1183–1194

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Jern P, Coffin JM (2008) Effects of retroviruses on host genome function. Annu Rev Genet 42:709–732

    Article  PubMed  CAS  Google Scholar 

  • Jha AR, Nixon DF, Rosenberg MG, Martin JN, Deeks SG et al (2011) Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans. PLoS One 6:e20234

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ji X, Zhao S (2008) DA and Xiao—two giant and composite LTR-retrotransposon-like elements identified in the human genome. Genomics 91:249–258

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kassiotis G (2014) Endogenous retroviruses and the development of cancer. J Immunol 192:1343–1349

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kelley LA, Sternberg MJ (2009) Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 4:363–371

    Article  PubMed  CAS  Google Scholar 

  • Kent WJ (2002) BLAT—the BLAST-like alignment tool. Genome Res 12:656

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  PubMed  CAS  Google Scholar 

  • Lange T, Deininger MW (2010) Molecular diagnostics in chronic myeloid leukemia. Expert Opin Med Diagn 4:113–124

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee YK, Chew A, Phan H, Greenhalgh DG, Cho K (2008) Genome-wide expression profiles of endogenous retroviruses in lymphoid tissues and their biological properties. Virology 373:263–273

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lee Y-J, Jeong B-H, Choi E-K, Kim Y-S (2013) Involvement of endogenous retroviruses in prion diseases. Pathogens 2:533–543

    Article  Google Scholar 

  • Leis J, Baltimore D, Bishop JM, Coffin J, Fleissner E et al (1988) Standardized and simplified nomenclature for proteins common to all retroviruses. J Virol 62:1808–1809

    PubMed  CAS  PubMed Central  Google Scholar 

  • Li X, Slife J, Patel N, Zhao S (2009) Stepwise evolution of two giant composite LTR-retrotransposon-like elements DA and Xiao. BMC Evol Biol 9:128

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lindeskog M, Medstrand P, Cunningham AA, Blomberg J (1998) Coamplification and dispersion of adjacent human endogenous retroviral HERV-H and HERV-E elements; presence of spliced hybrid transcripts in normal leukocytes. Virology 244:219–229

    Article  PubMed  CAS  Google Scholar 

  • Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS et al (1999) Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73:152–160

    PubMed  CAS  PubMed Central  Google Scholar 

  • López-Sánchez P, Costas JC, Naveira HF (2005) Paleogenomic record of the extinction of human endogenous retrovirus ERV9. J Virol 79:6997–7004

    Article  PubMed  PubMed Central  Google Scholar 

  • Mills RE, Bennett EA, Iskow RC, Devine SE (2007) Which transposable elements are active in the human genome? Trends Genet 23:183–191

    Article  PubMed  CAS  Google Scholar 

  • Moyes D, Griffiths DJ, Venables PJ (2007) Insertional polymorphisms: a new lease of life for endogenous retroviruses in human disease. Trends Genet 23:326–333

    Article  PubMed  CAS  Google Scholar 

  • Nissen KK, Laska MJ, Hansen B, Terkelsen T, Villesen P et al (2013) Endogenous retroviruses and multiple sclerosis—new pieces to the puzzle. BMC Neurol 13:111

    Article  PubMed  PubMed Central  Google Scholar 

  • Ogasawara H, Hishikawa T, Sekigawa I, Hashimoto H, Yamamoto N, Maruyama N (2000) Sequence analysis of human endogenous retrovirus clone 4-1 in systemic lupus erythematosus. Autoimmunity 33:15–21

    Article  PubMed  CAS  Google Scholar 

  • Piotrowski PC, Duriagin S, Jagodzinski PP (2005) Expression of human endogenous retrovirus clone 4-1 may correlate with blood plasma concentration of anti-U1 RNP and anti-Sm nuclear antibodies. Clin Rheumatol 24:620–624

    Article  PubMed  Google Scholar 

  • Prusty BK, zur Hausen H, Schmidt R, Kimmel R, de Villiers EM (2008) Transcription of HERV-E and HERV-E-related sequences in malignant and non-malignant human haematopoietic cells. Virology 382:37–45

    Article  PubMed  CAS  Google Scholar 

  • Repaske R, O’Neill RR, Steele PE, Martin MA (1983) Characterization and partial nucleotide sequence of endogenous type C retrovirus segments in human chromosomal DNA. Proc Natl Acad Sci USA 80:678–682

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Repaske R, Steele PE, O’Neill RR, Rabson AB, Martin MA (1985) Nucleotide sequence of a full-length human endogenous retroviral segment. J Virol 54:764–772

    PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Schneider AM, Duffield AS, Symer DE, Burns KH (2009) Roles of retrotransposons in benign and malignant hematologic disease. Cellscience 6:121–145

    PubMed  PubMed Central  Google Scholar 

  • Seifarth W, Frank O, Zeilfelder U, Spiess B, Greenwood AD et al (2005) Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus—specific microarray. J Virol 79:341–352

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Shin W, Lee J, Son SY, Ahn K, Kim HS, Han K (2013) Human-specific HERV-K insertion causes genomic variations in the human genome. PLoS One 8:e60605

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Smit AF (2008) HERVE_a - ERV1 endogenous retrovirus from Catarrhini. Direct submission to Repbase Update. http://www.girinst.org/repbase/index.html

  • Steele PE, Rabson AB, Bryan T, Martin MA (1984) Distinctive termini characterize two families of human endogenous retroviral sequences. Science 225:943–947

    Article  PubMed  CAS  Google Scholar 

  • Takahashi Y, Harashima N, Kajigaya S, Yokoyama H, Cherkasova E et al (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 Invest 118:1099–1109

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  PubMed  CAS  Google Scholar 

  • Taruscio D, Floridia G, Zoraqi GK, Mantovani A, Falbo V (2002) Organization and integration sites in the human genome of endogenous retroviral sequences belonging to HERV-E family. Mamm Genome 13:216–222

    Article  PubMed  CAS  Google Scholar 

  • Verstovsek S (2009) Preclinical and clinical experience with dasatinib in Philadelphia chromosome-negative leukemias and myeloid disorders. Leuk Res 33:617–623

    Article  PubMed  Google Scholar 

  • Voisset C, Weiss RA, Griffiths DJ (2008) Human RNA “rumor” viruses: the search for novel human retroviruses in chronic disease. Microbiol Mol Biol Rev 72:157–196

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Volkman HE, Stetson DB (2014) The enemy within: endogenous retroelements and autoimmune disease. Nat Immunol 15:415–422

    Article  PubMed  CAS  Google Scholar 

  • Yang Z (1998) Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 15:568–573

    Article  PubMed  CAS  Google Scholar 

  • Yi JM, Kim HS (2006) Molecular evolution of the HERV-E family in primates. Arch Virol 151:1107–1116

    Article  PubMed  CAS  Google Scholar 

  • Yi JM, Kim HS (2007) Molecular phylogenetic analysis of the human endogenous retrovirus E (HERV-E) family in human tissues and human cancers. Genes Genet Syst 82:89–98

    Article  PubMed  CAS  Google Scholar 

  • Young GR, Eksmond U, Salcedo R, Alexopoulou L, Stoye JP, Kassiotis G (2012) Resurrection of endogenous retroviruses in antibody-deficient mice. Nature 491:774–778

    PubMed  CAS  PubMed Central  Google Scholar 

  • Young GR, Stoye JP, Kassiotis G (2013) Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis. BioEssays 35:794–803

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank C. Phillips and. M. V. Lareu for kindly letting us use their copy of the HGDP-CEPH Human Genome Diversity Panel.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Grupo de Investigación en Bioloxía Evolutiva, Departamento de Bioloxía Celular e Molecular, Centro de Investigaciones Científicas Avanzadas (CICA), Universidade da Coruña, 15071, A Coruña, Spain

    Horacio Naveira & José Luis Abal-Fabeiro

  2. Grupo de Medicina Xenómica, Departamento de Anatomía Patolóxica e Ciencias Forenses, Centro de Investigación en Medicina Molecular e Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, 15782, A Coruña, Spain

    Xabier Bello, José Luis Abal-Fabeiro & Xulio Maside

Authors
  1. Horacio Naveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xabier Bello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Luis Abal-Fabeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xulio Maside
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Horacio Naveira.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Table S1. Full-length proviral insertions of the ERVE family in the human genome. (PDF 51 kb)

10709_2014_9789_MOESM2_ESM.pdf

Figure S1. Phylogenetic relationships within the ERVE family based on the analysis of gag, pr, rt and rh gene nucleotide sequences. (PDF 1051 kb)

10709_2014_9789_MOESM3_ESM.pdf

Figure S2. Multiple nucleotide alignment of HCML-ARV with the consensus of subfamily VIIa and the orthologous copies of provirus 022319 in humans and chimpanzees. (PDF 87 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Naveira, H., Bello, X., Abal-Fabeiro, J.L. et al. Evidence for the persistence of an active endogenous retrovirus (ERVE) in humans. Genetica 142, 451–460 (2014). https://doi.org/10.1007/s10709-014-9789-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10709-014-9789-y

Keywords

Search

Navigation