Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1994 Aug;68(8):5100–5107. doi: 10.1128/jvi.68.8.5100-5107.1994

Different abilities of Friend murine leukemia virus (MuLV) and Moloney MuLV to induce promonocytic leukemia are due to determinants in both psi-gag-PR and env regions.

R Mukhopadhyaya 1, J Richardson 1, V Nazarov 1, A Corbin 1, R Koller 1, M Sitbon 1, L Wolff 1
PMCID: PMC236453  PMID: 7518530

Abstract

Moloney murine leukemia virus (M-MuLV) is capable of inducing promonocytic leukemia in 50% of adult BALB/c mice that have received peritoneal injections of pristane, but Friend MuLV strain 57 (F-MuLV) is nonleukemogenic under similar conditions. It was shown earlier that these differences could not be mapped to the U3 region of the virus long terminal repeat, indicating the probable influence of structural genes and/or R-U5 sequences. In this study, reciprocal chimeras containing exchanged structural genes and R-U5 sequences from these two closely related viruses were analyzed for differences in ability to induce disease. Results showed that two regions of F-MuLV, psi-gag-PR and env, when substituted for those of M-MuLV were dramatically disease attenuating. The 5'-most region, which is widely distributed, overlaps with the 5' end of the env intron and includes the RNA packaging region, psi, the entire gag coding region, and the viral protease coding region (PR) of pol. It was also found that reciprocal constructs having substitutions of both of these regions of M-MuLV in an F-MuLV background allowed full reestablishment of promonocytic leukemia. These leukemias were positive for c-myb rearrangements which are characteristic of M-MuLV-induced promonocytic leukemias. Neither region alone, however, was sufficient to produce disease with a greater incidence than 13%. Further studies demonstrated that the inability of viruses with psi, gag, PR, or env sequences from F-MuLV to induce leukemia in this model system was not due to their inability to replicate in hematopoietic tissue, to integrate into the c-myb locus early on after infection in vivo, or to express gag-myb mRNA characteristic of M-MuLV-induced preleukemic cells and acute leukemia.

Full text

PDF

Images in this article

5103Image
on p.5103
5104Image
on p.5104
5105Image
on p.5105

Selected References

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

  1. Arrigo S., Yun M., Beemon K. cis-acting regulatory elements within gag genes of avian retroviruses. Mol Cell Biol. 1987 Jan;7(1):388–397. doi: 10.1128/mcb.7.1.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bender T. P., Kuehl W. M. Murine myb protooncogene mRNA: cDNA sequence and evidence for 5' heterogeneity. Proc Natl Acad Sci U S A. 1986 May;83(10):3204–3208. doi: 10.1073/pnas.83.10.3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bösze Z., Thiesen H. J., Charnay P. A transcriptional enhancer with specificity for erythroid cells is located in the long terminal repeat of the Friend murine leukemia virus. EMBO J. 1986 Jul;5(7):1615–1623. doi: 10.1002/j.1460-2075.1986.tb04404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Celander D., Haseltine W. A. Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses. Nature. 1984 Nov 8;312(5990):159–162. doi: 10.1038/312159a0. [DOI] [PubMed] [Google Scholar]
  5. Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chatis P. A., Holland C. A., Silver J. E., Frederickson T. N., Hopkins N., Hartley J. W. A 3' end fragment encompassing the transcriptional enhancers of nondefective Friend virus confers erythroleukemogenicity on Moloney leukemia virus. J Virol. 1984 Oct;52(1):248–254. doi: 10.1128/jvi.52.1.248-254.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen I. S., McLaughlin J., Golde D. W. Long terminal repeats of human T-cell leukaemia virus II genome determine target cell specificity. Nature. 1984 May 17;309(5965):276–279. doi: 10.1038/309276a0. [DOI] [PubMed] [Google Scholar]
  8. Chesebro B., Wehrly K. Different murine cell lines manifest unique patterns of interference to superinfection by murine leukemia viruses. Virology. 1985 Feb;141(1):119–129. doi: 10.1016/0042-6822(85)90188-6. [DOI] [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Corbin A., Sitbon M. Protection against retroviral diseases after vaccination is conferred by interference to superinfection with attenuated murine leukemia viruses. J Virol. 1993 Sep;67(9):5146–5152. doi: 10.1128/jvi.67.9.5146-5152.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DesGroseillers L., Jolicoeur P. Mapping the viral sequences conferring leukemogenicity and disease specificity in Moloney and amphotropic murine leukemia viruses. J Virol. 1984 Nov;52(2):448–456. doi: 10.1128/jvi.52.2.448-456.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DesGroseillers L., Rassart E., Jolicoeur P. Thymotropism of murine leukemia virus is conferred by its long terminal repeat. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eiden M. V., Farrell K., Warsowe J., Mahan L. C., Wilson C. A. Characterization of a naturally occurring ecotropic receptor that does not facilitate entry of all ecotropic murine retroviruses. J Virol. 1993 Jul;67(7):4056–4061. doi: 10.1128/jvi.67.7.4056-4061.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ferre F., Garduno F. Preparation of crude cell extract suitable for amplification of RNA by the polymerase chain reaction. Nucleic Acids Res. 1989 Mar 11;17(5):2141–2141. doi: 10.1093/nar/17.5.2141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goff S., Traktman P., Baltimore D. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase. J Virol. 1981 Apr;38(1):239–248. doi: 10.1128/jvi.38.1.239-248.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Golemis E., Li Y., Fredrickson T. N., Hartley J. W., Hopkins N. Distinct segments within the enhancer region collaborate to specify the type of leukemia induced by nondefective Friend and Moloney viruses. J Virol. 1989 Jan;63(1):328–337. doi: 10.1128/jvi.63.1.328-337.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Golub E. I., Kim H., Volsky D. J. Transfection of DNA into adherent cells by DEAE-dextran/DMSO method increases drastically if the cells are removed from surface and treated in suspension. Nucleic Acids Res. 1989 Jun 26;17(12):4902–4902. doi: 10.1093/nar/17.12.4902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kawasaki E. S., Clark S. S., Coyne M. Y., Smith S. D., Champlin R., Witte O. N., McCormick F. P. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5698–5702. doi: 10.1073/pnas.85.15.5698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McNally M. T., Gontarek R. R., Beemon K. Characterization of Rous sarcoma virus intronic sequences that negatively regulate splicing. Virology. 1991 Nov;185(1):99–108. doi: 10.1016/0042-6822(91)90758-4. [DOI] [PubMed] [Google Scholar]
  20. Nason-Burchenal K., Wolff L. Activation of c-myb is an early bone-marrow event in a murine model for acute promonocytic leukemia. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1619–1623. doi: 10.1073/pnas.90.4.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oliff A. I., Hager G. L., Chang E. H., Scolnick E. M., Chan H. W., Lowy D. R. Transfection of molecularly cloned Friend murine leukemia virus DNA yields a highly leukemogenic helper-independent type C virus. J Virol. 1980 Jan;33(1):475–486. doi: 10.1128/jvi.33.1.475-486.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Richardson J., Corbin A., Pozo F., Orsoni S., Sitbon M. Sequences responsible for the distinctive hemolytic potentials of Friend and Moloney murine leukemia viruses are dispersed but confined to the psi-gag-PR region. J Virol. 1993 Sep;67(9):5478–5486. doi: 10.1128/jvi.67.9.5478-5486.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Shen-Ong G. L., Wolff L. Moloney murine leukemia virus-induced myeloid tumors in adult BALB/c mice: requirement of c-myb activation but lack of v-abl involvement. J Virol. 1987 Dec;61(12):3721–3725. doi: 10.1128/jvi.61.12.3721-3725.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Shoemaker C., Goff S., Gilboa E., Paskind M., Mitra S. W., Baltimore D. Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3932–3936. doi: 10.1073/pnas.77.7.3932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sitbon M., Ellerbrok H., Pozo F., Nishio J., Hayes S. F., Evans L. H., Chesebro B. Sequences in the U5-gag-pol region influence early and late pathogenic effects of Friend and Moloney murine leukemia viruses. J Virol. 1990 May;64(5):2135–2140. doi: 10.1128/jvi.64.5.2135-2140.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sitbon M., Nishio J., Wehrly K., Lodmell D., Chesebro B. Use of a focal immunofluorescence assay on live cells for quantitation of retroviruses: distinction of host range classes in virus mixtures and biological cloning of dual-tropic murine leukemia viruses. Virology. 1985 Feb;141(1):110–118. doi: 10.1016/0042-6822(85)90187-4. [DOI] [PubMed] [Google Scholar]
  29. Sitbon M., Sola B., Evans L., Nishio J., Hayes S. F., Nathanson K., Garon C. F., Chesebro B. Hemolytic anemia and erythroleukemia, two distinct pathogenic effects of Friend MuLV: mapping of the effects to different regions of the viral genome. Cell. 1986 Dec 26;47(6):851–859. doi: 10.1016/0092-8674(86)90800-7. [DOI] [PubMed] [Google Scholar]
  30. Sitbon M., d'Auriol L., Ellerbrok H., André C., Nishio J., Perryman S., Pozo F., Hayes S. F., Wehrly K., Tambourin P. Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5932–5936. doi: 10.1073/pnas.88.13.5932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stocking C., Kollek R., Bergholz U., Ostertag W. Point mutations in the U3 region of the long terminal repeat of Moloney murine leukemia virus determine disease specificity of the myeloproliferative sarcoma virus. Virology. 1986 Aug;153(1):145–149. doi: 10.1016/0042-6822(86)90015-2. [DOI] [PubMed] [Google Scholar]
  32. Thiesen H. J., Bösze Z., Henry L., Charnay P. A DNA element responsible for the different tissue specificities of Friend and Moloney retroviral enhancers. J Virol. 1988 Feb;62(2):614–618. doi: 10.1128/jvi.62.2.614-618.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Verdin E., Becker N., Bex F., Droogmans L., Burny A. Identification and characterization of an enhancer in the coding region of the genome of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4874–4878. doi: 10.1073/pnas.87.12.4874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wolff L., Koller R. Regions of the Moloney murine leukemia virus genome specifically related to induction of promonocytic tumors. J Virol. 1990 Jan;64(1):155–160. doi: 10.1128/jvi.64.1.155-160.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wolff L., Mushinski J. F., Shen-Ong G. L., Morse H. C., 3rd A chronic inflammatory response. Its role in supporting the development of c-myb and c-myc related promonocytic and monocytic tumors in BALB/c mice. J Immunol. 1988 Jul 15;141(2):681–689. [PubMed] [Google Scholar]
  36. Wolff L., Nason-Burchenal K. Retrovirus-induced tumors whose development is facilitated by a chronic immune response: a comparison of two tumors committed to the monocytic lineage. Curr Top Microbiol Immunol. 1989;149:79–87. doi: 10.1007/978-3-642-74623-9_7. [DOI] [PubMed] [Google Scholar]
  37. Yoshimura F. K., Davison B., Chaffin K. Murine leukemia virus long terminal repeat sequences can enhance gene activity in a cell-type-specific manner. Mol Cell Biol. 1985 Oct;5(10):2832–2835. doi: 10.1128/mcb.5.10.2832. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES