Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203

Thymotropism of murine leukemia virus is conferred by its long terminal repeat.

L DesGroseillers, E Rassart, P Jolicoeur
PMCID: PMC384005  PMID: 6308605

Abstract

Several murine leukemia viruses (MuLV) replicate efficiently in the thymus (T+) of the mouse, whereas others are unable to replicate (T-) in this organ. To map the region of the viral genome harboring the sequences responsible for this thymotropic phenotype, we constructed viral DNA recombinants in vitro between cloned infectious viral DNAs from T- BALB/c N-tropic MuLV and from T+ BALB/c B-tropic MuLV or AKR Gross passage A MuLV. (N- and B-tropic refer to the Fv-1 host range of MuLV.) Infectious recombinant MuLVs, recovered from murine cells microinjected with these recombinant DNAs, were injected into newborn mice to test their ability to replicate in the thymus. We found that the long terminal repeat from the T+ BALB/c B-tropic or AKR Gross passage A MuLV genome was sufficient to allow replication of recombinant MuLVs in the thymus. Our sequence data suggested that the U3 tandem direct repeat was responsible for this effect. These results suggest a new role for the U3 long terminal repeat in the replication of MuLV in specific differentiated target cells.

Full text

PDF
4203

Selected References

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

  1. Bedigian H. G., Taylor B. A., Meier H. Expression of murine leukemia viruses in the highly lymphomatous BXH-2 recombinant inbred mouse strain. J Virol. 1981 Aug;39(2):632–640. doi: 10.1128/jvi.39.2.632-640.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cloyd M. W., Hartley J. W., Rowe W. P. Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. J Exp Med. 1980 Mar 1;151(3):542–552. doi: 10.1084/jem.151.3.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Declève A., Lieberman M., Ihle J. N., Kaplan H. S. Biological and serological characterization of radiation leukemia virus. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4675–4679. doi: 10.1073/pnas.73.12.4675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Declève A., Sato C., Lieberman M., Kaplan H. S. Selective thymic localization of murine leukemia virus-related antigens in C57BL-Ka mice after inoculation with radiation virus. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3124–3128. doi: 10.1073/pnas.71.8.3124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ebbesen P., Rask-Nielsen R., Hartley J. W., Rowe W. P. Murine reticulum cell neoplasms type B (Hodgkin's-like lesions) induced in BALB-c mice with field isolates of murine leukemia virus. Eur J Cancer. 1973 Mar;9(3):173–179. doi: 10.1016/s0014-2964(73)80016-7. [DOI] [PubMed] [Google Scholar]
  6. Greenberger J. S., Stephenson J. R., Moloney W. C., Aaronson S. A. Different hematological diseases induced by type C viruses chemically activated from embryo cells of different mouse strains. Cancer Res. 1975 Jan;35(1):245–252. [PubMed] [Google Scholar]
  7. Grunstein M., Hogness D. S. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. doi: 10.1073/pnas.72.10.3961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gruss P., Dhar R., Khoury G. Simian virus 40 tandem repeated sequences as an element of the early promoter. Proc Natl Acad Sci U S A. 1981 Feb;78(2):943–947. doi: 10.1073/pnas.78.2.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hartley J. W., Rowe W. P., Capps W. I., Huebner R. J. Isolation of naturally occurring viruses of the murine leukemia virus group in tissue culture. J Virol. 1969 Feb;3(2):126–132. doi: 10.1128/jvi.3.2.126-132.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hartley J. W., Rowe W. P. Clonal cells lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses. Virology. 1975 May;65(1):128–134. doi: 10.1016/0042-6822(75)90013-6. [DOI] [PubMed] [Google Scholar]
  11. Hartley J. W., Rowe W. P., Huebner R. J. Host-range restrictions of murine leukemia viruses in mouse embryo cell cultures. J Virol. 1970 Feb;5(2):221–225. doi: 10.1128/jvi.5.2.221-225.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jolicoeur P., Rosenberg N., Cotellessa A., Baltimore D. Leukemogenicity of clonal isolates of murine leukemia viruses. J Natl Cancer Inst. 1978 Jun;60(6):1473–1476. doi: 10.1093/jnci/60.6.1473. [DOI] [PubMed] [Google Scholar]
  13. Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levinson B., Khoury G., Vande Woude G., Gruss P. Activation of SV40 genome by 72-base pair tandem repeats of Moloney sarcoma virus. Nature. 1982 Feb 18;295(5850):568–572. doi: 10.1038/295568a0. [DOI] [PubMed] [Google Scholar]
  15. Lung M. L., Hartley J. W., Rowe W. P., Hopkins N. H. Large RNase T1-resistant oligonucleotides encoding p15E and the U3 region of the long terminal repeat distinguish two biological classes of mink cell focus-forming type C viruses of inbred mice. J Virol. 1983 Jan;45(1):275–290. doi: 10.1128/jvi.45.1.275-290.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  17. Moreau P., Hen R., Wasylyk B., Everett R., Gaub M. P., Chambon P. The SV40 72 base repair repeat has a striking effect on gene expression both in SV40 and other chimeric recombinants. Nucleic Acids Res. 1981 Nov 25;9(22):6047–6068. doi: 10.1093/nar/9.22.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nowinski R. C., Hays E. F. Oncogenicity of AKR endogenous leukemia viruses. J Virol. 1978 Jul;27(1):13–18. doi: 10.1128/jvi.27.1.13-18.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Oliff A., Linemeyer D., Ruscetti S., Lowe R., Lowy D. R., Scolnick E. Subgenomic fragment of molecular cloned Friend murine leukemia virus DNA contains the gene(s) responsible for Friend murine leukemia virus-induced disease. J Virol. 1980 Sep;35(3):924–936. doi: 10.1128/jvi.35.3.924-936.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Peters R. L., Spahn G. J., Rabstein L. S., Kelloff G. J., Huebner R. J. Neoplasm induction by murine type-C viruses passaged directly from spontaneous non-lymphoreticular tumours. Nat New Biol. 1973 Jul 25;244(134):103–105. doi: 10.1038/newbio244103a0. [DOI] [PubMed] [Google Scholar]
  21. Rassart E., DesGroseillers L., Jolicoeur P. Molecular cloning of B- and N-tropic endogenous BALB/c murine leukemia virus circular DNA intermediates: isolation and characterization of infectious recombinant clones. J Virol. 1981 Jul;39(1):162–171. doi: 10.1128/jvi.39.1.162-171.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rassart E., Jolicoeur P. Restriction endonuclease mapping of unintegrated viral DNA of B- and N-tropic BALB/c murine leukemia virus. J Virol. 1980 Sep;35(3):812–823. doi: 10.1128/jvi.35.3.812-823.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rassart E., Sankar-Mistry P., Lemay G., DesGroseillers L., Jolicoeur P. New class of leukemogenic ecotropic recombinant murine leukemia virus isolated from radiation-induced thymomas of C57BL/6 mice. J Virol. 1983 Feb;45(2):565–575. doi: 10.1128/jvi.45.2.565-575.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Robinson H. L., Blais B. M., Tsichlis P. N., Coffin J. M. At least two regions of the viral genome determine the oncogenic potential of avian leukosis viruses. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1225–1229. doi: 10.1073/pnas.79.4.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  26. Storms R. K., Holowachuck E. W., Friesen J. D. Genetic complementation of the Saccharomyces cerevisiae leu2 gene by the Escherichia coli leuB gene. Mol Cell Biol. 1981 Sep;1(9):836–842. doi: 10.1128/mcb.1.9.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tsichlis P. N., Coffin J. M. Role of the C region in relative growth rates of endogenous and exogenous avian oncoviruses. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1123–1132. doi: 10.1101/sqb.1980.044.01.121. [DOI] [PubMed] [Google Scholar]
  28. Van Beveren C., Rands E., Chattopadhyay S. K., Lowy D. R., Verma I. M. Long terminal repeat of murine retroviral DNAs: sequence analysis, host-proviral junctions, and preintegration site. J Virol. 1982 Feb;41(2):542–556. doi: 10.1128/jvi.41.2.542-556.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Varmus H. E. Form and function of retroviral proviruses. Science. 1982 May 21;216(4548):812–820. doi: 10.1126/science.6177038. [DOI] [PubMed] [Google Scholar]
  30. Villemur R., Rassart E., DesGroseillers L., Jolicoeur P. Molecular cloning of viral DNA from leukemogenic Gross passage A murine leukemia virus and nucleotide sequence of its long terminal repeat. J Virol. 1983 Feb;45(2):539–546. doi: 10.1128/jvi.45.2.539-546.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ware L. M., Axelrad A. A. Inherited resistance to N- and B-tropic murine leukemia viruses in vitro: evidence that congenic mouse strains SIM and SIM.R differ at the Fv-1 locus. Virology. 1972 Nov;50(2):339–348. doi: 10.1016/0042-6822(72)90385-6. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES