Retroviral Repeat Sequences


Retroviral repeats are genomic DNA segments that have structural or sequence similarity to the integrated (proviral) forms of vertebrate retroviruses. Such sequences are termed endogenous retrovirusā€like elements or, more commonly, endogenous retroviruses.

Keywords: endogenous retroviruses; long terminal repeats; repetitive DNA; evolution

Figure 1.

Prototypical structure of an integrated retrovirus or provirus. The identical LTRs, shown as open boxes, flank an internal region containing the three genes of simple retroviruses. gag encodes structural proteins, pol encodes RNase H, reverse transcriptase and endonuclease, and env encodes the viral envelope coat protein that recognizes a cell surface receptor and enables the virus to infect the cell. Noninfectious LTR‐containing retrotransposons have a similar structure but lack the env gene. LTRs typically begin with TG and end with CA, which are part of a short inverted repeat shown as arrows within the open boxes. Each LTR also contains a transcriptional enhancer, promoter and polyadenylation signal. The tRNA primer binding site (PBS) is a sequence of 18–21 bp that is complementary to the 3′ end of a specific tRNA. This site binds a tRNA molecule that is necessary to prime viral reverse transcription. Cellular DNA is shown as a dotted line and the cellular sequence of 4–6 bp that is duplicated on integration is shown as two thick arrows bordering the provirus. A solitary LTR, created by recombination between two LTRs, is also bordered by a direct repeat of 4–6 bp. The diagram is not drawn to scale.

Figure 2.

Relationship of exogenous and human endogenous retroviruses. The tree depicts the relationship between selected exogenous retroviruses and entries in Repbase or previously reported HERV sequences in a 550‐bp region encoding the reverse transcriptase of the retroviral polymerase. Sequences fall into one of three (I–III) classes. Exogenous retroviruses are indicated with a filled circle. HIV: human immunodeficiency virus; HSRV: human spumavirus; HTLV: human T‐cell leukemia virus. The branch length corresponds to the sequence distance indicted below the class II sequences. (This tree was constructed using programs CLUSTALW, and DNADIST and KITSCH of PHYLIP.)

Figure 3.

Examples of expansion patterns of three HERV groups during primate evolution. Unfilled ovals represent the approximate time of the initial fixation of the HERV element in the primate lineage. Filled ovals indicate approximate windows in time of different expansions of the elements, where the widths of the oval correspond roughly to the total copy number of the HERVs and the solitary LTRs at the time indicated on the left. An arrow indicates a major burst or expansion resulting in a significantly higher copy number of the elements. The left axis indicates the time in millions of years (Myr) from the present. The right axis indicates the approximate time that different lineages diverged from humans. The data shown are derived mainly from Anderssen et al., Medstrand and Mager and Costas and Naveira .



Anderssen S, Sjottem E, Svineng G and Johansen T (1997) Comparative analyses of LTRs of the ERV‐H family of primate‐specific retrovirus‐like elements isolated from marmoset, African green monkey and man. Virology 234: 14–30.

Andersson ML, Lindeskog M, Medstrand P, et al. (1999) Diversity of human endogenous retrovirus class II‐like sequences. Journal of General Virology 80: 255–260.

Bénit L, Lallemand JP, Casella JF, Philippe H and Heidmann T (1999) ERV‐L elements: a family of endogenous retrovirus‐like elements active throughout the evolution of mammals. Journal of Virology 73: 3301–3308.

Brosius J (1999) Genomes were forged by massive bombardments with retroelements and retrosequences. Genetica 107: 209–238.

Costas J and Naveira H (2000) Evolutionary history of the human endogenous retrovirus family ERV9. Molecular Biology and Evolution 17: 320–330.

Johnson WE and Coffin JM (1999) Constructing primate phylogenies from ancient retrovirus sequences. Proceedings of the National Academy of Sciences of the United States of America 96: 10254–10260.

Jurka J (2000) Repbase update: a database and an electronic journal of repetitive elements. Trends in Genetics 16: 418–420.

Löwer R, Löwer J and Kurth R (1996) The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proceedings of the National Academy of Sciences of the United States of America 93: 5177–5184.

Medstrand P, Landry JR and Mager DL (2001) Long terminal repeats are used as alternative promoters for the endothelin B receptor and apolipoprotein C1 genes in humans. Journal of Biological Chemistry 276: 1896–1903.

Medstrand P and Mager DL (1998) Human‐specific integrations of the HERV‐K endogenous retrovirus family. Journal of Virology 72: 9782–9787.

Medstrand P, Van De Lagemaat LN and Mager DL (2002) Retroelement distributions in the human genome: variations associated with age and proximity to genes. Genome Research 12: 1483–1495.

Mi S, Lee X, Li XP, et al. (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403: 785–789.

Smit AF (1993) Identification of a new, abundant superfamily of mammalian LTR‐transposons. Nucleic Acids Research 21: 1863–1872.

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

Turner G, Barbulescu M, Su M, et al. (2001) Insertional polymorphisms of full‐length endogenous retroviruses in humans. Current Biology 11: 1531–1535.

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Further Reading

Andersson G, Svensson AC, Setterblad N and Rask L (1998) Retroelements in the human MHC class II region. Trends in Genetics 14: 109–114.

Bock M and Stoye JP (2000) Endogenous retroviruses and the human germline. Current Opinion in Genetics and Development 10: 651–655.

Boeke JD and Stoye JP (1997) Retrotransposons, endogenous retroviruses, and the evolution of retroelements. In: Coffin JM, Hughes SH and Varmus HE (eds.) Retroviruses, pp. 343–435. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Boese A, Sauter M, Galli U, et al. (2000) Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein. Oncogene 19: 4328–4336.

Dawkins R, Leelayuwat C, Gaudieri S, et al. (1999) Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease. Immunological Reviews 167: 275–304.

Hughes JF and Coffin JM (2001) Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nature Genetics 29: 487–489.

Löwer R (1999) The pathogenic potential of endogenous retroviruses: facts and fantasies. Trends in Microbiology 7: 350–356.

Sverdlov ED (2000) Retroviruses and primate evolution. BioEssays 22: 161–171.

Towers G, Bock M, Martin S, et al. (2000) A conserved mechanism of retrovirus restriction in mammals. Proceedings of the National Academy of Sciences of the United States of America 97: 12295–12299.

Whiteclaw E and Martin DIK (2001) Retrotransposons as epigenetic mediators of phenotypic variation in mammals. Nature Genetics 27: 361–365.

Web Links

Human Endogenous Retroviruses Database

National Center for Biotechnology Information (NCBI)


NCBI Taxonomy Browser‐post/Taxonomy/wgetorg?mode=Undef&id=11632&lvl=3&genome=1&srchmode=1

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Mager, Dixie L, and Medstrand, Patrik(Sep 2005) Retroviral Repeat Sequences. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005062]