Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Oct;69(10):6408–6416. doi: 10.1128/jvi.69.10.6408-6416.1995

Retrovirus-like particles released from the human breast cancer cell line T47-D display type B- and C-related endogenous retroviral sequences.

W Seifarth 1, H Skladny 1, F Krieg-Schneider 1, A Reichert 1, R Hehlmann 1, C Leib-Mösch 1
PMCID: PMC189540  PMID: 7545247

Abstract

The human mammary carcinoma cell line T47-D releases retrovirus-like particles of type B morphology in a steroid-dependent manner (I. Keydar, T. Ohno, R. Nayak, R. Sweet, F. Simoni, F. Weiss, S. Karby, R. Mesa-Tejada, and S. Spiegelman, Proc. Natl. Acad. Sci. USA 81:4188-4192, 1984). Furthermore, reverse transcriptase (RT) activity is found to be associated with particle preparations. Using a set of degenerate primers derived from a conserved region of retroviral pol genes, we repeatedly amplified three different retroviral sequences (MLN, FRD, and FTD) from purified T47-D particles in several RT-PCR experiments. Screening of a human genomic library and Southern blot analysis revealed that these sequences are of endogenous origin. ERV-MLN represents a multicopy family of human endogenous retroviral elements (HERVs) with two closely related copies and up to 20 more distantly related members. In contrast, ERV-FRD and ERV-FTD comprise only one copy and five to seven related elements per haploid human genome. DNA sequence analysis of the proviral pol region of ERV-MLN revealed an uninterrupted stretch of 241 amino acids that shows 65% identity with the RT of the type B-related HERV designated HERV-K10. ERV-FRD and ERV-FTD are defective type C-related HERVs. The pol gene of ERV-FRD displays a nucleotide homology of 54% to the gibbon ape leukemia virus, and the pol gene of ERV-FTD is about 67% homologous to members of the RTVL-I family of HERVs. Our results thus indicate that the retroviral particles released by the breast cancer cell line T47-D are probably generated by complementation of several endogenous proviruses and can package retroviral transcripts of different origins.

Full Text

The Full Text of this article is available as a PDF (591.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banki K., Maceda J., Hurley E., Ablonczy E., Mattson D. H., Szegedy L., Hung C., Perl A. Human T-cell lymphotropic virus (HTLV)-related endogenous sequence, HRES-1, encodes a 28-kDa protein: a possible autoantigen for HTLV-I gag-reactive autoantibodies. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1939–1943. doi: 10.1073/pnas.89.5.1939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boller K., König H., Sauter M., Mueller-Lantzsch N., Löwer R., Löwer J., Kurth R. Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. Virology. 1993 Sep;196(1):349–353. doi: 10.1006/viro.1993.1487. [DOI] [PubMed] [Google Scholar]
  3. Brack-Werner R., Leib-Mösch C., Werner T., Erfle V., Hehlmann R. Human endogenous retrovirus-like sequences. Haematol Blood Transfus. 1989;32:464–477. doi: 10.1007/978-3-642-74621-5_81. [DOI] [PubMed] [Google Scholar]
  4. Brodsky I., Foley B., Haines D., Johnston J., Cuddy K., Gillespie D. Expression of HERV-K proviruses in human leukocytes. Blood. 1993 May 1;81(9):2369–2374. [PubMed] [Google Scholar]
  5. Delassus S., Sonigo P., Wain-Hobson S. Genetic organization of gibbon ape leukemia virus. Virology. 1989 Nov;173(1):205–213. doi: 10.1016/0042-6822(89)90236-5. [DOI] [PubMed] [Google Scholar]
  6. Etzerodt M., Mikkelsen T., Pedersen F. S., Kjeldgaard N. O., Jørgensen P. The nucleotide sequence of the Akv murine leukemia virus genome. Virology. 1984 Apr 15;134(1):196–207. doi: 10.1016/0042-6822(84)90285-x. [DOI] [PubMed] [Google Scholar]
  7. Garry R. F., Fermin C. D., Hart D. J., Alexander S. S., Donehower L. A., Luo-Zhang H. Detection of a human intracisternal A-type retroviral particle antigenically related to HIV. Science. 1990 Nov 23;250(4984):1127–1129. doi: 10.1126/science.1701273. [DOI] [PubMed] [Google Scholar]
  8. Gupta S., Ribak C. E., Gollapudi S., Kim C. H., Salahuddin S. Z. Detection of a human intracisternal retroviral particle associated with CD4+ T-cell deficiency. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7831–7835. doi: 10.1073/pnas.89.16.7831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haltmeier M., Seifarth W., Blusch J., Erfle V., Hehlmann R., Leib-Mösch C. Identification of S71-related human endogenous retroviral sequences with full-length pol genes. Virology. 1995 Jun 1;209(2):550–560. doi: 10.1006/viro.1995.1287. [DOI] [PubMed] [Google Scholar]
  10. Hatzoglou M., Hodgson C. P., Mularo F., Hanson R. W. Efficient packaging of a specific VL30 retroelement by psi 2 cells which produce MoMLV recombinant retroviruses. Hum Gene Ther. 1990 Winter;1(4):385–397. doi: 10.1089/hum.1990.1.4-385. [DOI] [PubMed] [Google Scholar]
  11. Johnson M. S., McClure M. A., Feng D. F., Gray J., Doolittle R. F. Computer analysis of retroviral pol genes: assignment of enzymatic functions to specific sequences and homologies with nonviral enzymes. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7648–7652. doi: 10.1073/pnas.83.20.7648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Johnson P. M., Lyden T. W., Mwenda J. M. Endogenous retroviral expression in the human placenta. Am J Reprod Immunol. 1990 Aug;23(4):115–120. doi: 10.1111/j.1600-0897.1990.tb00683.x. [DOI] [PubMed] [Google Scholar]
  13. Keydar I., Chen L., Karby S., Weiss F. R., Delarea J., Radu M., Chaitcik S., Brenner H. J. Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer. 1979 May;15(5):659–670. doi: 10.1016/0014-2964(79)90139-7. [DOI] [PubMed] [Google Scholar]
  14. Keydar I., Ohno T., Nayak R., Sweet R., Simoni F., Weiss F., Karby S., Mesa-Tejada R., Spiegelman S. Properties of retrovirus-like particles produced by a human breast carcinoma cell line: immunological relationship with mouse mammary tumor virus proteins. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4188–4192. doi: 10.1073/pnas.81.13.4188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krieg A. M., Gourley M. F., Klinman D. M., Perl A., Steinberg A. D. Heterogeneous expression and coordinate regulation of endogenous retroviral sequences in human peripheral blood mononuclear cells. AIDS Res Hum Retroviruses. 1992 Dec;8(12):1991–1998. doi: 10.1089/aid.1992.8.1991. [DOI] [PubMed] [Google Scholar]
  16. La Mantia G., Maglione D., Pengue G., Di Cristofano A., Simeone A., Lanfrancone L., Lania L. Identification and characterization of novel human endogenous retroviral sequences prefentially expressed in undifferentiated embryonal carcinoma cells. Nucleic Acids Res. 1991 Apr 11;19(7):1513–1520. doi: 10.1093/nar/19.7.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Larsson E., Kato N., Cohen M. Human endogenous proviruses. Curr Top Microbiol Immunol. 1989;148:115–132. doi: 10.1007/978-3-642-74700-7_4. [DOI] [PubMed] [Google Scholar]
  18. Larsson E., Nilsson B. O., Sundström P., Widéhn S. Morphological and microbiological signs of endogenous C-virus in human oocytes. Int J Cancer. 1981 Nov 15;28(5):551–557. doi: 10.1002/ijc.2910280504. [DOI] [PubMed] [Google Scholar]
  19. Levy J. A. Murine xenotropic type C viruses. III. Phenotypic mixing with avian leukosis and sarcoma viruses. Virology. 1977 Apr;77(2):811–825. doi: 10.1016/0042-6822(77)90501-3. [DOI] [PubMed] [Google Scholar]
  20. Lusso P., di Marzo Veronese F., Ensoli B., Franchini G., Jemma C., DeRocco S. E., Kalyanaraman V. S., Gallo R. C. Expanded HIV-1 cellular tropism by phenotypic mixing with murine endogenous retroviruses. Science. 1990 Feb 16;247(4944):848–852. doi: 10.1126/science.2305256. [DOI] [PubMed] [Google Scholar]
  21. Lyden T. W., Johnson P. M., Mwenda J. M., Rote N. S. Ultrastructural characterization of endogenous retroviral particles isolated from normal human placentas. Biol Reprod. 1994 Jul;51(1):152–157. doi: 10.1095/biolreprod51.1.152. [DOI] [PubMed] [Google Scholar]
  22. Löwer J., Wondrak E. M., Kurth R. Genome analysis and reverse transcriptase activity of human teratocarcinoma-derived retroviruses. J Gen Virol. 1987 Nov;68(Pt 11):2807–2815. doi: 10.1099/0022-1317-68-11-2807. [DOI] [PubMed] [Google Scholar]
  23. Löwer R., Boller K., Hasenmaier B., Korbmacher C., Müller-Lantzsch N., Löwer J., Kurth R. Identification of human endogenous retroviruses with complex mRNA expression and particle formation. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4480–4484. doi: 10.1073/pnas.90.10.4480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Löwer R., Löwer J., Tondera-Koch C., Kurth R. A general method for the identification of transcribed retrovirus sequences (R-U5 PCR) reveals the expression of the human endogenous retrovirus loci HERV-H and HERV-K in teratocarcinoma cells. Virology. 1993 Feb;192(2):501–511. doi: 10.1006/viro.1993.1066. [DOI] [PubMed] [Google Scholar]
  25. Löwer R., Tönjes R. R., Korbmacher C., Kurth R., Löwer J. Identification of a Rev-related protein by analysis of spliced transcripts of the human endogenous retroviruses HTDV/HERV-K. J Virol. 1995 Jan;69(1):141–149. doi: 10.1128/jvi.69.1.141-149.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maeda N., Kim H. S. Three independent insertions of retrovirus-like sequences in the haptoglobin gene cluster of primates. Genomics. 1990 Dec;8(4):671–683. doi: 10.1016/0888-7543(90)90254-r. [DOI] [PubMed] [Google Scholar]
  27. Medstrand P., Blomberg J. 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. 1993 Nov;67(11):6778–6787. doi: 10.1128/jvi.67.11.6778-6787.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Medstrand P., Lindeskog M., Blomberg J. Expression of human endogenous retroviral sequences in peripheral blood mononuclear cells of healthy individuals. J Gen Virol. 1992 Sep;73(Pt 9):2463–2466. doi: 10.1099/0022-1317-73-9-2463. [DOI] [PubMed] [Google Scholar]
  29. Mondal H., Hofschneider P. H. Isolation and characterization of retrovirus-like elements from normal human fetuses. Int J Cancer. 1982 Sep 15;30(3):281–287. doi: 10.1002/ijc.2910300305. [DOI] [PubMed] [Google Scholar]
  30. Moore D. H., Charney J., Kramarsky B., Lasfargues E. Y., Sarkar N. H., Brennan M. J., Burrows J. H., Sirsat S. M., Paymaster J. C., Vaidya A. B. Search for a human breast cancer virus. Nature. 1971 Feb 26;229(5287):611–614. doi: 10.1038/229611a0. [DOI] [PubMed] [Google Scholar]
  31. Moore R., Dixon M., Smith R., Peters G., Dickson C. Complete nucleotide sequence of a milk-transmitted mouse mammary tumor virus: two frameshift suppression events are required for translation of gag and pol. J Virol. 1987 Feb;61(2):480–490. doi: 10.1128/jvi.61.2.480-490.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mueller-Lantzsch N., Sauter M., Weiskircher A., Kramer K., Best B., Buck M., Grässer F. Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease. AIDS Res Hum Retroviruses. 1993 Apr;9(4):343–350. doi: 10.1089/aid.1993.9.343. [DOI] [PubMed] [Google Scholar]
  33. Ng S. Y., Gunning P., Eddy R., Ponte P., Leavitt J., Shows T., Kedes L. Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol. 1985 Oct;5(10):2720–2732. doi: 10.1128/mcb.5.10.2720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ono M., Kawakami M., Ushikubo H. Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line T47D. J Virol. 1987 Jun;61(6):2059–2062. doi: 10.1128/jvi.61.6.2059-2062.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ono M., Toh H., Miyata T., Awaya T. Nucleotide sequence of the Syrian hamster intracisternal A-particle gene: close evolutionary relationship of type A particle gene to types B and D oncovirus genes. J Virol. 1985 Aug;55(2):387–394. doi: 10.1128/jvi.55.2.387-394.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ono M., Yasunaga T., Miyata T., Ushikubo H. Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome. J Virol. 1986 Nov;60(2):589–598. doi: 10.1128/jvi.60.2.589-598.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Repaske R., Steele P. E., O'Neill R. R., Rabson A. B., Martin M. A. Nucleotide sequence of a full-length human endogenous retroviral segment. J Virol. 1985 Jun;54(3):764–772. doi: 10.1128/jvi.54.3.764-772.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sauter M., Schommer S., Kremmer E., Remberger K., Dölken G., Lemm I., Buck M., Best B., Neumann-Haefelin D., Mueller-Lantzsch N. Human endogenous retrovirus K10: expression of Gag protein and detection of antibodies in patients with seminomas. J Virol. 1995 Jan;69(1):414–421. doi: 10.1128/jvi.69.1.414-421.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Scadden D. T., Fuller B., Cunningham J. M. Human cells infected with retrovirus vectors acquire an endogenous murine provirus. J Virol. 1990 Jan;64(1):424–427. doi: 10.1128/jvi.64.1.424-427.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Scolnick E. M., Vass W. C., Howk R. S., Duesberg P. H. Defective retrovirus-like 30S RNA species of rat and mouse cells are infectious if packaged by type C helper virus. J Virol. 1979 Mar;29(3):964–972. doi: 10.1128/jvi.29.3.964-972.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sherwin S. A., Rapp U. R., Benveniste R. E., Sen A., Todaro G. J. Rescue of endogenous 30S retroviral sequences from mouse cells by baboon type C virus. J Virol. 1978 May;26(2):257–264. doi: 10.1128/jvi.26.2.257-264.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Shih A., Misra R., Rush M. G. Detection of multiple, novel reverse transcriptase coding sequences in human nucleic acids: relation to primate retroviruses. J Virol. 1989 Jan;63(1):64–75. doi: 10.1128/jvi.63.1.64-75.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  45. Spector D. H., Wade E., Wright D. A., Koval V., Clark C., Jaquish D., Spector S. A. Human immunodeficiency virus pseudotypes with expanded cellular and species tropism. J Virol. 1990 May;64(5):2298–2308. doi: 10.1128/jvi.64.5.2298-2308.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Takeuchi Y., Simpson G., Vile R. G., Weiss R. A., Collins M. K. Retroviral pseudotypes produced by rescue of a Moloney murine leukemia virus vector by C-type, but not D-type, retroviruses. Virology. 1992 Feb;186(2):792–794. doi: 10.1016/0042-6822(92)90049-u. [DOI] [PubMed] [Google Scholar]
  47. Tamura T. A. Provirus of M7 baboon endogenous virus: nucleotide sequence of the gag-pol region. J Virol. 1983 Jul;47(1):137–145. doi: 10.1128/jvi.47.1.137-145.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tautz D., Renz M. An optimized freeze-squeeze method for the recovery of DNA fragments from agarose gels. Anal Biochem. 1983 Jul 1;132(1):14–19. doi: 10.1016/0003-2697(83)90419-0. [DOI] [PubMed] [Google Scholar]
  49. Vogetseder W., Dumfahrt A., Mayersbach P., Schönitzer D., Dierich M. P. Antibodies in human sera recognizing a recombinant outer membrane protein encoded by the envelope gene of the human endogenous retrovirus K. AIDS Res Hum Retroviruses. 1993 Jul;9(7):687–694. doi: 10.1089/aid.1993.9.687. [DOI] [PubMed] [Google Scholar]
  50. Weiss R. A., Wong A. L. Phenotypic mixing between avian and mammalian RNA tumor viruses: I. Envelope pseudotypes of Rous sarcoma virus. Virology. 1977 Feb;76(2):826–834. doi: 10.1016/0042-6822(77)90262-8. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES