Cited by 309Chromosomal and Genetic VariationsGenomic variations and chromosomal abnormalitiesEvolution and Genetic Dynamics

Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements

Open access
Dewannieux, Marie, Harper, Francis, Richaud, Aurélien, Letzelter, Claire, Ribet, David, Pierron, Gérard, Heidmann, Thierry·2006·Genome Research

Abstract

Human Endogenous Retroviruses are expected to be the remnants of ancestral infections of primates by active retroviruses that have thereafter been transmitted in a Mendelian fashion. Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny. We also show that this element amplifies via an extracellular pathway involving reinfection, at variance with the non-LTR-retrotransposons (LINEs, SINEs) or LTR-retrotransposons, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. We also show that in vitro recombinations among present-day human HERV-K (also known as ERVK) loci can similarly generate functional HERV-K elements, indicating that human cells still have the potential to produce infectious retroviruses.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/gr.5565706

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There is no fully functional HERV-K in the human genome, but a number of HERV-K proviruses are capable of making one or several of the viral proteins.

    “There is no fully functional HERV-K in the human genome, but a number of HERV-K proviruses are capable of making one or several of the viral proteins”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Dewannieux et al. 2006

    The Abstract says that no HERV-K provirus able to produce infectious particles had yet been described, and that several loci have complete viral-protein coding sequences. But it does not establish that no fully functional HERV-K exists in the human genome; the Discussion says some human alleles might still be functional. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • Recombination between three defective HERV-K (HML2) proviruses has been shown, at least in vitro, to generate an infectious retrovirus.

    “and, furthermore, recombination between three defective HERV-K (HML2) proviruses has been shown, at least in vitro, to generate an infectious retrovirus 84.”
  • Reconstruction of a consensus HERV-K (HML2) provirus by assembly and alignment of all complete but defective HERV-K (HML2) proviruses resulted in a replication-competent recombinant retrovirus.

    “Interestingly, reconstruction of a consensus HERV-K (HML2) provirus by assembly and alignment of all of the complete, but defective HERV-K (HML2) proviruses resulted in a replication-competent recombinant retrovirus 84,85.”
  • Engineered recombinant HERV-K constructs that contain all open reading frames are capable of viral transmission in cell culture.

    “Engineered recombinant HERV-K constructs that contain all open reading frames are capable of viral transmission in cell culture”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 38 · Cited by 309

Research works printed but not linked: 34

  1. Bannert N., Kurth R., Kurth R. Retroelements and the human genome: New perspectives on an old relation. Proc. Natl. Acad. Sci. 2004;101:14572–14579. doi: 10.1073/pnas.0404838101. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  2. Belshaw R., Pereira V., Katzourakis A., Talbot G., Paces J., Burt A., Tristem M., Pereira V., Katzourakis A., Talbot G., Paces J., Burt A., Tristem M., Katzourakis A., Talbot G., Paces J., Burt A., Tristem M., Talbot G., Paces J., Burt A., Tristem M., Paces J., Burt A., Tristem M., Burt A., Tristem M., Tristem M. Long-term reinfection of the human genome by endogenous retroviruses. Proc. Natl. Acad. Sci. 2004;25:25. doi: 10.1073/pnas.0307800101. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  3. Belshaw R., Dawson A.L., Woolven-Allen J., Redding J., Burt A., Tristem M., Dawson A.L., Woolven-Allen J., Redding J., Burt A., Tristem M., Woolven-Allen J., Redding J., Burt A., Tristem M., Redding J., Burt A., Tristem M., Burt A., Tristem M., Tristem M. Genomewide screening reveals high levels of insertional polymorphism in the human endogenous retrovirus family HERV-K(HML2): Implications for present-day activity. J. Virol. 2005;79:12507–12514. doi: 10.1128/JVI.79.19.12507-12514.2005. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  4. Benit L., Dessen P., Heidmann T., Dessen P., Heidmann T., Heidmann T. Identification, phylogeny, and evolution of retroviral elements based on their envelope genes. J. Virol. 2001;75:11709–11719. doi: 10.1128/JVI.75.23.11709-11719.2001. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  5. Bieda K., Hoffmann A., Boller K., Hoffmann A., Boller K., Boller K. Phenotypic heterogeneity of human endogenous retrovirus particles produced by teratocarcinoma cell lines. J. Gen. Virol. 2001;82:591–596. doi: 10.1099/0022-1317-82-3-591. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  6. Boeke J.D., Stoye J.P., Stoye J.P. Retrotransposons, endogenous retroviruses, and the evolution of retroelements. In: Coffin J.M., et al., editors. Retroviruses. Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY: 1997. pp. 343–435. [PubMed] [Google Scholar]
  7. Boller K., König H., Sauter M., Mueller-Lantzsch N., Löwer R., Löwer J., Kurth R., König H., Sauter M., Mueller-Lantzsch N., Löwer R., Löwer J., Kurth R., Sauter M., Mueller-Lantzsch N., Löwer R., Löwer J., Kurth R., Mueller-Lantzsch N., Löwer R., Löwer J., Kurth R., Löwer R., Löwer J., Kurth R., Löwer J., Kurth R., Kurth R. Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. Virology. 1993;196:349–353. doi: 10.1006/viro.1993.1487. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  8. Brown P.O. Integration. In: Coffin J.M., et al., editors. Retroviruses. Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY: 1997. pp. 161–204. [Google Scholar]
  9. Bushman F.D. Targeting survival. Integration site selection by retroviruses and LTR-retrotransposons. Cell. 2003;115:135–138. doi: 10.1016/s0092-8674(03)00760-8. [DOI] [PubMed] [Google Scholar] · DOI
  10. de Parseval N., Lazar V., Bénit L., Casella J., Heidmann T., Lazar V., Bénit L., Casella J., Heidmann T., Bénit L., Casella J., Heidmann T., Casella J., Heidmann T., Heidmann T. Survey of human genes of retroviral origin: Identification and transcriptome of the genes with coding capacity for complete envelope proteins. J. Virol. 2003;77:10414–10422. doi: 10.1128/JVI.77.19.10414-10422.2003. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  11. Dewannieux M., Heidmann T., Heidmann T. LINEs, SINEs and processed pseudogenes: Parasitic strategies for genome modeling. Cytogenet. Genome Res. 2005;110:35–48. doi: 10.1159/000084936. [DOI] [PubMed] [Google Scholar] · DOI
  12. Dewannieux M., Esnault C., Heidmann T., Esnault C., Heidmann T., Heidmann T. LINE-mediated retrotransposition of marked Alu sequences. Nat. Genet. 2003;35:41–48. doi: 10.1038/ng1223. [DOI] [PubMed] [Google Scholar] · DOI
  13. Dirksen E., Levy J., Levy J. Virus-like particles in placentas from normal individuals and patients with systemic lupus erythematosus. J. Natl. Cancer Inst. 1977;59:1187–1192. doi: 10.1093/jnci/59.4.1187. [DOI] [PubMed] [Google Scholar] · DOI
  14. Esnault C., Casella J.F., Heidmann T., Casella J.F., Heidmann T., Heidmann T. A Tetrahymena thermophila ribozyme-based indicator gene to detect transposition of marked retroelements in mammalian cells. Nucleic Acids Res. 2002;30:e49. doi: 10.1093/nar/30.11.e49. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  15. Goff S. Retrovirus restriction factors. Mol. Cell. 2004;16:849–859. doi: 10.1016/j.molcel.2004.12.001. [DOI] [PubMed] [Google Scholar] · DOI
  16. Harris R.S., Liddament M.T., Liddament M.T. Retroviral restriction by APOBEC proteins. Nat. Rev. Immunol. 2004;4:868–877. doi: 10.1038/nri1489. [DOI] [PubMed] [Google Scholar] · DOI
  17. Hughes J.F., Coffin J.M., Coffin J.M. Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: Implications for human and viral evolution. Proc. Natl. Acad. Sci. 2004;101:1668–1672. doi: 10.1073/pnas.0307885100. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  18. Hughes J.F., Coffin J.M., Coffin J.M. Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome. Genetics. 2005;12:12. doi: 10.1534/genetics.105.043976. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  19. Jolly C., Sattentau Q.J., Sattentau Q.J. Retroviral spread by induction of virological synapses. Traffic. 2004;5:643–650. doi: 10.1111/j.1600-0854.2004.00209.x. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  20. Kalter S.S., Helmke R.J., Heberling R.L., Panigel M., Fowler A.K., Strickland J.E., Hellman A., Helmke R.J., Heberling R.L., Panigel M., Fowler A.K., Strickland J.E., Hellman A., Heberling R.L., Panigel M., Fowler A.K., Strickland J.E., Hellman A., Panigel M., Fowler A.K., Strickland J.E., Hellman A., Fowler A.K., Strickland J.E., Hellman A., Strickland J.E., Hellman A., Hellman A. C-Type particles in normal human placentas. J. Natl. Cancer Inst. 1973;50:1081–1084. doi: 10.1093/jnci/50.4.1081. [DOI] [PubMed] [Google Scholar] · DOI
  21. Kazazian H.H., Jr. Mobile elements: Drivers of genome evolution. Science. 2004;303:1626–1632. doi: 10.1126/science.1089670. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  22. Lavie L., Kitova M., Maldener E., Meese E., Mayer J., Kitova M., Maldener E., Meese E., Mayer J., Maldener E., Meese E., Mayer J., Meese E., Mayer J., Mayer J. CpG methylation directly regulates transcriptional activity of the human endogenous retrovirus family HERV-K(HML-2) J. Virol. 2005;79:876–883. doi: 10.1128/JVI.79.2.876-883.2005. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  23. Löwer R., Löwer J., Kurth R., Löwer J., Kurth R., Kurth R. The viruses in all of us: Characteristics and biological significance of human endogenous retrovirus sequences. Proc. Natl. Acad. Sci. 1996;93:5177–5184. doi: 10.1073/pnas.93.11.5177. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  24. Mayer J., Sauter M., Racz A., Scherer D., Mueller-Lantzsch N., Meese E., Sauter M., Racz A., Scherer D., Mueller-Lantzsch N., Meese E., Racz A., Scherer D., Mueller-Lantzsch N., Meese E., Scherer D., Mueller-Lantzsch N., Meese E., Mueller-Lantzsch N., Meese E., Meese E. An almost-intact human endogenous retrovirus K on human chromosome 7. Nat. Genet. 1999;21:257–258. doi: 10.1038/6766. [DOI] [PubMed] [Google Scholar] · DOI
  25. Medstrand P., Mager D.L., Mager D.L. Human-specific integrations of the HERV-K endogenous retrovirus family. J. Virol. 1998;72:9782–9787. doi: 10.1128/jvi.72.12.9782-9787.1998. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  26. Muster T., Waltenberger A., Grassauer A., Hirschl S., Caucig P., Romirer I., Fodinger D., Seppele H., Schanab O., Magin-Lachmann C., Waltenberger A., Grassauer A., Hirschl S., Caucig P., Romirer I., Fodinger D., Seppele H., Schanab O., Magin-Lachmann C., Grassauer A., Hirschl S., Caucig P., Romirer I., Fodinger D., Seppele H., Schanab O., Magin-Lachmann C., Hirschl S., Caucig P., Romirer I., Fodinger D., Seppele H., Schanab O., Magin-Lachmann C., Caucig P., Romirer I., Fodinger D., Seppele H., Schanab O., Magin-Lachmann C., Romirer I., Fodinger D., Seppele H., Schanab O., Magin-Lachmann C., Fodinger D., Seppele H., Schanab O., Magin-Lachmann C., Seppele H., Schanab O., Magin-Lachmann C., Schanab O., Magin-Lachmann C., Magin-Lachmann C., et al. An endogenous retrovirus derived from human melanoma cells. Cancer Res. 2003;63:8735–8741. [PubMed] [Google Scholar]
  27. Pyra H., Boni J., Schupbach J., Boni J., Schupbach J., Schupbach J. Ultrasensitive retrovirus detection by a reverse transcriptase assay based on product enhancement. Proc. Natl. Acad. Sci. 1994;91:1544–1548. doi: 10.1073/pnas.91.4.1544. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  28. Reus K., Mayer J., Sauter M., Scherer D., Muller-Lantzsch N., Meese E., Mayer J., Sauter M., Scherer D., Muller-Lantzsch N., Meese E., Sauter M., Scherer D., Muller-Lantzsch N., Meese E., Scherer D., Muller-Lantzsch N., Meese E., Muller-Lantzsch N., Meese E., Meese E. Genomic organization of the human endogenous retrovirus HERV-K(HML-2.HOM) (ERVK6) on chromosome 7. Genomics. 2001;72:314–320. doi: 10.1006/geno.2000.6488. [DOI] [PubMed] [Google Scholar] · DOI
  29. Ruda V.M., Akopov S.B., Trubetskoy D.O., Manuylov N.L., Vetchinova A.S., Zavalova L.L., Nikolaev L.G., Sverdlov E.D., Akopov S.B., Trubetskoy D.O., Manuylov N.L., Vetchinova A.S., Zavalova L.L., Nikolaev L.G., Sverdlov E.D., Trubetskoy D.O., Manuylov N.L., Vetchinova A.S., Zavalova L.L., Nikolaev L.G., Sverdlov E.D., Manuylov N.L., Vetchinova A.S., Zavalova L.L., Nikolaev L.G., Sverdlov E.D., Vetchinova A.S., Zavalova L.L., Nikolaev L.G., Sverdlov E.D., Zavalova L.L., Nikolaev L.G., Sverdlov E.D., Nikolaev L.G., Sverdlov E.D., Sverdlov E.D. Tissue specificity of enhancer and promoter activities of a HERV-K(HML-2) LTR. Virus Res. 2004;104:11–16. doi: 10.1016/j.virusres.2004.02.036. [DOI] [PubMed] [Google Scholar] · DOI
  30. Steinhuber S., Brack M., Hunsmann G., Schwelberger H., Dierich M.P., Vogetseder W., Brack M., Hunsmann G., Schwelberger H., Dierich M.P., Vogetseder W., Hunsmann G., Schwelberger H., Dierich M.P., Vogetseder W., Schwelberger H., Dierich M.P., Vogetseder W., Dierich M.P., Vogetseder W., Vogetseder W. Distribution of human endogenous retrovirus HERV-K genomes in humans and different primates. Hum. Genet. 1995;96:188–192. doi: 10.1007/BF00207377. [DOI] [PubMed] [Google Scholar] · DOI
  31. Stoye J.P., Moroni C., Coffin J.M., Moroni C., Coffin J.M., Coffin J.M. Virological events leading to spontaneous AKR thymomas. J. Virol. 1991;65:1273–1285. doi: 10.1128/jvi.65.3.1273-1285.1991. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  32. Turner G., Barbulescu M., Su M., Jensen-Seaman M.I., Kidd K.K., Lenz J., Barbulescu M., Su M., Jensen-Seaman M.I., Kidd K.K., Lenz J., Su M., Jensen-Seaman M.I., Kidd K.K., Lenz J., Jensen-Seaman M.I., Kidd K.K., Lenz J., Kidd K.K., Lenz J., Lenz J. Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr. Biol. 2001;11:1531–1535. doi: 10.1016/s0960-9822(01)00455-9. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  33. Villesen P., Aagaard L., Wiuf C., Pedersen F.S., Aagaard L., Wiuf C., Pedersen F.S., Wiuf C., Pedersen F.S., Pedersen F.S. Identification of endogenous retroviral reading frames in the human genome. Retrovirology. 2004;1:32. doi: 10.1186/1742-4690-1-32. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  34. Wilkinson D.A., Mager D.L., Leong J.A.C., Mager D.L., Leong J.A.C., Leong J.A.C. Endogenous human retroviruses. In: Levy J.A., editor. The retroviridae. Plenum Press; New York: 1994. pp. 465–535. [Google Scholar]

Authors
Dewannieux, M., Harper, F., Richaud, A., Letzelter, C., Ribet, D., Pierron, G., & Heidmann, T.
Affiliations
Centre National de la Recherche Scientifique (FR)
Venue
Genome Research
Published
2006-10-31
Volume
16
Issue
12
Pages
1548-1556
ISSN
1088-9051 (ISSN-L)
OpenAlex
W2135790438
Cited by
309
References
38
Citations by year
2026: 7 · 2025: 8 · 2024: 21 · 2023: 12 · 2022: 8 · 2021: 18 · 2020: 6 · 2019: 17 · 2018: 15 · 2017: 15 · 2016: 16 · 2015: 18 · 2014: 22 · 2013: 23 · 2012: 15
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Centre National de la Recherche Scientifique
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
HERV-K, human endogenous retroviruses, retroviral reactivation, retrotransposition, recombination, retroviral integration, retroviral evolution
MeSH terms
Amino Acid Sequence, Cell Line, Gene Amplification, Humans, Polymorphism, Genetic, Proviruses, Recombination, Genetic, Transfection, Genome, Human, Mutagenesis, Insertional, Consensus Sequence, Virus Integration, Retroelements, Evolution, Molecular, Computational Biology, Amino Acid Substitution, Endogenous Retroviruses

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review