Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1980 Jun 1;151(6):1477–1492. doi: 10.1084/jem.151.6.1477

Anemia- and polycythemia-inducing isolates of Friend spleen focus- forming virus. Biological and molecular evidence for two distinct viral genomes

PMCID: PMC2185875  PMID: 6929880

Abstract

Two distinct clones of Friend spleen focus-forming virus (SFFV), differing in their erythroleukemic potential, are described. These isolates have been cloned free of their associated helper viruses and shown to be replication-defective. Both SFFV isolates have been rescued from rat fibroblast nonproducer cell clones with cloned replication- competent viruses, F-MuLVA and F-MuLVP, obtained from the anemia- or polycythemia-inducing isolates of Friend virus complex, respectively. These rescued viruses induce a rapid proliferative disease associated with the appearance of macroscopic spleen foci and splenomegaly. In addition, each is subject to regulation by the W, Steel (Sl), and Fv-2 host gene loci. These two isolates of SFFV can, however, be distinguished by both biological and molecular criteria. Friend SFFVP induces a rapid polycythemia associated with the appearance of large numbers of erythropoietin (EPO)-independent erythroid colony-forming cells in the marrow and spleen. In contrast, SFFVA induces a rapid anemia associated with a progressive decrease in the number of EPO- dependent erythroid colony-forming cells in marrow, and a rapid increase in the number of EPO-dependent erythroid colony-forming cells in spleen. Furthermore, the nature of the disease induced by the two isolates of SFFV is independent of the Friend helper virus: SFFVP, rescued from a nonproducer cell clone with either F-MuLVA or F0MuLVP, induced a polycythemic transformation, whereas SFFVA, rescued with either F-MuLVA or F-MuLVP, induced an anemic transformation. The two Friend SFFV isolates can also be discriminated on the basis of translational products encoded by their gag and env genes: SFFVP encodes the amino-terminal gag-gene protein p15, whereas SFFVA encodes the gag-gene proteins p15, p12, and p30. In addition, the SFFV isolates encode nonidentical 55,000-mol wt env gene-related proteins that can be distinguished by analysis of their methionine-containing tryptic peptides.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

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

  1. AXELRAD A. A., STEEVES R. A. ASSAY FOR FRIEND LEUKEMIA VIRUS: RAPID QUANTITATIVE METHOD BASED ON ENUMERATION OF MACROSCOPIC SPLEEN FOCI IN MICE. Virology. 1964 Nov;24:513–518. doi: 10.1016/0042-6822(64)90199-0. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M., Stephenson J. R., Aaronson S. A. gag Gene of mammalian type-C RNA tumour viruses. Nature. 1976 Aug 12;262(5569):554–559. doi: 10.1038/262554a0. [DOI] [PubMed] [Google Scholar]
  3. Barbacid M., Troxler D. H., Scolnick E. M., Aaronson S. A. Analysis of translational products of Friend strain of spleen focus-forming virus. J Virol. 1978 Sep;27(3):826–830. doi: 10.1128/jvi.27.3.826-830.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bennett M., Steeves R. A., Cudkowicz G., Mirand E. A., Russell L. B. Mutant Sl alleles of mice affect susceptibility to Friend spleen focus-forming virus. Science. 1968 Nov 1;162(3853):564–565. doi: 10.1126/science.162.3853.564. [DOI] [PubMed] [Google Scholar]
  5. Bernstein A., Mak T. W., Stephenson J. R. The Friend virus genome: evidence for the stable association of MuLV sequences and sequences involved in erythroleukemic transformation. Cell. 1977 Sep;12(1):287–294. doi: 10.1016/0092-8674(77)90206-9. [DOI] [PubMed] [Google Scholar]
  6. Dresler S., Ruta M., Murray M. J., Kabat D. Glycoprotein encoded by the Friend spleen focus-forming virus. J Virol. 1979 May;30(2):564–575. doi: 10.1128/jvi.30.2.564-575.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FRIEND C. Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia. J Exp Med. 1957 Apr 1;105(4):307–318. doi: 10.1084/jem.105.4.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hasthorpe S., Bol S. Erythropoietin responses and physical characterization of erythroid progenitor cells in Rauscher virus infected BALB/c mice. J Cell Physiol. 1979 Jul;100(1):77–86. doi: 10.1002/jcp.1041000108. [DOI] [PubMed] [Google Scholar]
  9. Horoszewicz J. S., Leong S. S., Carter W. A. Friend leukemia: rapid development of erythropoietin-independent hematopoietic precursors. J Natl Cancer Inst. 1975 Jan;54(1):265–267. doi: 10.1093/jnci/54.1.265. [DOI] [PubMed] [Google Scholar]
  10. Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Liao S. K., Axelrad A. A. Erythropoietin-independent erythroid colony formation in vitro by hemopoietic cells of mice infected with friend virus. Int J Cancer. 1975 Mar 15;15(3):467–482. doi: 10.1002/ijc.2910150313. [DOI] [PubMed] [Google Scholar]
  12. Lilly F. Fv-2: identification and location of a second gene governing the spleen focus response to Friend leukemia virus in mice. J Natl Cancer Inst. 1970 Jul;45(1):163–169. [PubMed] [Google Scholar]
  13. MCCULLOCH E. A., SIMINOVITCH L., TILL J. E. SPLEEN-COLONY FORMATION IN ANEMIC MICE OF GENOTYPE WW. Science. 1964 May 15;144(3620):844–846. doi: 10.1126/science.144.3620.844. [DOI] [PubMed] [Google Scholar]
  14. METCALF D., FURTH J., BUFFETT R. F. Pathogenesis of mouse leukemia caused by Friend virus. Cancer Res. 1959 Jan;19(1):52–58. [PubMed] [Google Scholar]
  15. MacDonald M. E., Mak T. W., Bernstein A. Erythroleukemia induction by replication-competent type C viruses cloned from the anemia- and polycythemia-inducing isolates of Friend leukemia virus. J Exp Med. 1980 Jun 1;151(6):1493–1503. doi: 10.1084/jem.151.6.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mak T. W., Axelrad A. A., Bernstein A. Fv-2 locus controls expression of Friend spleen focus-forming virus-specific sequences in normal and infected mice. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5809–5812. doi: 10.1073/pnas.76.11.5809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McCool D., Mak T. W., Bernstein A. Cellular regulation in Friend virus induced erythroleukemia. Studies with anemic mice of genotype Sl/Sld. J Exp Med. 1979 Apr 1;149(4):837–846. doi: 10.1084/jem.149.4.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McCulloch E. A., Siminovitch L., Till J. E., Russell E. S., Bernstein S. E. The cellular basis of the genetically determined hemopoietic defect in anemic mice of genotype Sl-Sld. Blood. 1965 Oct;26(4):399–410. [PubMed] [Google Scholar]
  19. Mirand E. A. Murine viral-induced polycyhemia. Ann N Y Acad Sci. 1968 Mar 29;149(1):486–496. doi: 10.1111/j.1749-6632.1968.tb15187.x. [DOI] [PubMed] [Google Scholar]
  20. Mirand E. A., Steeves R. A., Avila L., Grace J. T., Jr Spleen focus formation by polycythemic strains of Friend leukemia virus. Proc Soc Exp Biol Med. 1968 Mar;127(3):900–904. doi: 10.3181/00379727-127-32831. [DOI] [PubMed] [Google Scholar]
  21. Mirand E. A., Steeves R. A., Lange R. D., Grace J. T., Jr Virus-induced polycythemia in mice: erythropoiesis without erythropoietin. Proc Soc Exp Biol Med. 1968 Jul;128(3):844–849. doi: 10.3181/00379727-128-33139. [DOI] [PubMed] [Google Scholar]
  22. Prasad I., Zouzias D., Basilico C. State of the viral DNA in rat cells transformed by polyoma virus. I. Virus rescue and the presence of nonintergrated viral DNA molecules. J Virol. 1976 May;18(2):436–444. doi: 10.1128/jvi.18.2.436-444.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reynolds R. K., Stephenson J. R. Intracistronic mapping of the murine type C viral gag gene by use of conditional lethal replication mutants. Virology. 1977 Sep;81(2):328–340. doi: 10.1016/0042-6822(77)90149-0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Ruscetti S., Linemeyer D., Field J., Troxler D., Scolnick E. Type-specific radioimmunoassays for the gp70s of mink cell focus-inducing murine leukemia viruses: expression of a cross-reacting antigen in cells infected with the Friend strain of the spleen focus-forming virus. J Exp Med. 1978 Sep 1;148(3):654–663. doi: 10.1084/jem.148.3.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stanners C. P., Eliceiri G. L., Green H. Two types of ribosome in mouse-hamster hybrid cells. Nat New Biol. 1971 Mar 10;230(10):52–54. doi: 10.1038/newbio230052a0. [DOI] [PubMed] [Google Scholar]
  27. Steeves R. A., Bennett M., Mirand E. A., Cudkowicz G. Genetic control by the W locus of susceptibility to (Friend) spleen focus-forming virus. Nature. 1968 Apr 27;218(5139):372–374. doi: 10.1038/218372a0. [DOI] [PubMed] [Google Scholar]
  28. Steeves R. A., Eckner R. J., Bennett M., Mirand E. A., Trudel P. J. Isolation and characterization of a lymphatic leukemia virus in the Friend virus complex. J Natl Cancer Inst. 1971 Jun;46(6):1209–1217. [PubMed] [Google Scholar]
  29. Steinheider G., Seidel H. J., Kreja L. Comparison of the biological effects of anemia inducing and polycythemia inducing Friend virus complex. Experientia. 1979 Sep 15;35(9):1173–1175. doi: 10.1007/BF01963269. [DOI] [PubMed] [Google Scholar]
  30. Stephenson J. R., Axelrad A. A., McLeod D. L., Shreeve M. M. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542–1546. doi: 10.1073/pnas.68.7.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stephenson J. R., Reynolds R. K., Devare S. G., Reynolds F. H. Biochemical and immunological properties of gag genecoded structural proteins of endogenous tyep C RNA tumor viruses of diverse mammalian species. J Biol Chem. 1977 Nov 10;252(21):7818–7825. [PubMed] [Google Scholar]
  32. Troxler D. H., Boyars J. K., Parks W. P., Scolnick E. M. Friend strain of spleen focus-forming virus: a recombinant between mouse type C ecotropic viral sequences and sequences related to xenotropic virus. J Virol. 1977 May;22(2):361–372. doi: 10.1128/jvi.22.2.361-372.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES