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. 1988 Feb;62(2):511–518. doi: 10.1128/jvi.62.2.511-518.1988

Loss of pathogenicity of spleen focus-forming virus after pseudotyping with Akv.

K S Jones 1, S Ruscetti 1, F Lilly 1
PMCID: PMC250562  PMID: 2826812

Abstract

Friend virus complex (FV), which comprises replication-competent Friend murine leukemia virus (FMuLV) plus replication-defective spleen focus-forming virus (SFFV), induces a multistage erythroleukemia. We have examined the role of replication-competent helper virus in the early and late stages of FV disease by replacing FMuLV, the native helper, with Akv, the endogenous ecotropic MuLV of AKR mice. SFFVP/FRE, an established fibroblast line nonproductively infected with the polycythemic strain of SFFV, was superinfected with FMuLV or with Akv. Although supernatants from these cells showed similar titers in the XC plaque assay, supernatants from Akv-infected SFFVP/FRE cells showed 100- to 5,000-fold less activity than did those from FMuLV-infected cells with respect to spleen focus induction in vivo. Since virions isolated from these two supernatants contained similar ratios of SFFV to helper virus genomic RNA, it did not appear that the difference was due to a relative inability of Akv to package SFFV. Although FMuLV- and Akv-rescued SFFV are equally infectious in a mouse fibroblast cell line (NIH 3T3), FMuLV-rescued SFFV was far more efficient in inducing erythroid bursts in cultured primary bone marrow cells. Adding Akv to preparations of FMuLV-rescued SFFV did not significantly interfere with burst induction. Helper-free SFFV induced 50- to 500-fold more spleen foci when coinjected with FMuLV than it did with Akv. Helper virus also affected mortality rates that reflect the late stage of the disease. When FMuLV- or Akv-rescued SFFV was injected into NIH Swiss mice at dosage levels adjusted to give equal numbers of spleen foci, all mice receiving FMuLV-rescued SFFV developed splenomegaly and died, whereas no mice receiving Akv-rescued SFFV died or developed detectable splenomegaly. When FMuLV was coinjected with Akv-rescued SFFV, the mortality rate rose from 0 to 100%. Injection of helper-free SFFV alone did not induce mortality, but coinjection of helper-free SFFV with FMuLV resulted in 100% mortality. Thus, the helper virus used to rescue SFFV plays at least a quantitatively important role in the early stage of FV disease and a crucial role in the late stage of the disease in vivo.

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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. Berger S. A., Sanderson N., Bernstein A., Hankins W. D. Induction of the early stages of Friend erythroleukemia with helper-free Friend spleen focus-forming virus. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6913–6917. doi: 10.1073/pnas.82.20.6913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Chesebro B., Wehrly K., Cloyd M., Britt W., Portis J., Collins J., Nishio J. Characterization of mouse monoclonal antibodies specific for Friend murine leukemia virus-induced erythroleukemia cells: friend-specific and FMR-specific antigens. Virology. 1981 Jul 15;112(1):131–144. doi: 10.1016/0042-6822(81)90619-x. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Evans L. H., Duesberg P. H., Troxler D. H., Scolnick E. M. Spleen focus-forming Friend virus: identification of genomic RNA and its relationship to helper virus RNA. J Virol. 1979 Jul;31(1):133–146. doi: 10.1128/jvi.31.1.133-146.1979. [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. Fagg B., Ostertag W. Friend erythroleukemia virus complex: role of viral components in modifying erythroid differentiation in mice. J Natl Cancer Inst. 1982 Mar;68(3):457–460. [PubMed] [Google Scholar]
  9. Faller D. V., Hopkins N. T1 oligonucleotide maps of N-, B-, and B leads to NB-tropic murine leukemia viruses derived from BALB/c. J Virol. 1978 Apr;26(1):143–152. doi: 10.1128/jvi.26.1.143-152.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Faller D. V., Hopkins N. T1 oligonucleotides that segregate with tropism and with properties of gp70 in recombinants between N- and B-tropic murine leukemia viruses. J Virol. 1978 Apr;26(1):153–158. doi: 10.1128/jvi.26.1.153-158.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  12. Hankins W. D., Kost T. A., Koury M. J., Krantz S. B. Erythroid bursts produced by Friend leukaemia virus in vitro. Nature. 1978 Nov 30;276(5687):506–508. doi: 10.1038/276506a0. [DOI] [PubMed] [Google Scholar]
  13. Hankins W. D., Troxler D. Polycythemia- and anemia-inducing erythroleukemia viruses exhibit differential erythroid transforming effects in vitro. Cell. 1980 Dec;22(3):693–699. doi: 10.1016/0092-8674(80)90545-0. [DOI] [PubMed] [Google Scholar]
  14. Holt C. A., Osorio K., Lilly F. Friend virus-specific cytotoxic T lymphocytes recognize both gag and env gene-encoded specificities. J Exp Med. 1986 Jul 1;164(1):211–226. doi: 10.1084/jem.164.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huang A. S., Besmer P., Chu L., Baltimore D. Growth of pseudotypes of vesicular stomatitis virus with N-tropic murine leukemia virus coats in cells resistant to N-tropic viruses. J Virol. 1973 Sep;12(3):659–662. doi: 10.1128/jvi.12.3.659-662.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Jolicoeur P., Baltimore D. Effect of Fv-1 gene product on synthesis of N-tropic and B-tropic murine leukemia viral RNA. Cell. 1976 Jan;7(1):33–39. doi: 10.1016/0092-8674(76)90252-x. [DOI] [PubMed] [Google Scholar]
  18. Jolicoeur P. The Fv-1 gene of the mouse and its control of murine leukemia virus replication. Curr Top Microbiol Immunol. 1979;86:67–122. doi: 10.1007/978-3-642-67341-2_3. [DOI] [PubMed] [Google Scholar]
  19. Kluge N. K., Ostertag W., Fusco A., Pennie S., Greenberger J. S. Multipotential hemopoietic cell lines isolated from stem cell cultures infected with Friend virus complex (MuLV + F-SFFV) show presence of MuLV but not F-SFFV. Leuk Res. 1986;10(2):187–193. doi: 10.1016/0145-2126(86)90041-x. [DOI] [PubMed] [Google Scholar]
  20. Koch W., Hunsmann G., Friedrich R. Nucleotide sequence of the envelope gene of Friend murine leukemia virus. J Virol. 1983 Jan;45(1):1–9. doi: 10.1128/jvi.45.1.1-9.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kost T. A., Koury M. J., Krantz S. B. Mature erythroid burst-forming units are target cells for Friend virus-induced erythroid bursts. Virology. 1981 Jan 30;108(2):309–317. doi: 10.1016/0042-6822(81)90439-6. [DOI] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. Lenz J., Crowther R., Straceski A., Haseltine W. Nucleotide sequence of the Akv env gene. J Virol. 1982 May;42(2):519–529. doi: 10.1128/jvi.42.2.519-529.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Linemeyer D. L., Menke J. G., Ruscetti S. K., Evans L. H., Scolnick E. M. Envelope gene sequences which encode the gp52 protein of spleen focus-forming virus are required for the induction of erythroid cell proliferation. J Virol. 1982 Jul;43(1):223–233. doi: 10.1128/jvi.43.1.223-233.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. MacDonald M. E., Reynolds F. H., Jr, Van de Ven W. J., Stephenson J. R., Mak T. W., Bernstein A. Anemia- and polycythemia-inducing isolates of Friend spleen focus-forming virus. Biological and molecular evidence for two distinct viral genomes. J Exp Med. 1980 Jun 1;151(6):1477–1492. doi: 10.1084/jem.151.6.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mann R., Mulligan R. C., Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. doi: 10.1016/0092-8674(83)90344-6. [DOI] [PubMed] [Google Scholar]
  27. Moreau-Gachelin F., D'Auriol L., Robert-Lezenes J., Galibert F., Tambourin P., Tavitian A. Analysis of integrated proviral DNA sequences with an octadecanucleotide probe designed for specific identification of spleen focus-forming virus in the mouse genome. J Virol. 1986 Jan;57(1):349–352. doi: 10.1128/jvi.57.1.349-352.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Moreau-Gachelin F., Robert-Lezenes J., Wendling F., Tavitian A., Tambourin P. Integration of spleen focus-forming virus proviruses in Friend tumor cells. J Virol. 1985 Jan;53(1):292–295. doi: 10.1128/jvi.53.1.292-295.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Pedersen F. S., Haseltine W. A. A micromethod for detailed characterization of high molecular weight RNA. Methods Enzymol. 1980;65(1):680–687. doi: 10.1016/s0076-6879(80)65066-6. [DOI] [PubMed] [Google Scholar]
  31. Rommelaere J., Donis-Keller H., Hopkins N. RNA sequencing provides evidence for allelism of determinants of the N-, B- or NB-tropism of murine leukemia viruses. Cell. 1979 Jan;16(1):43–50. doi: 10.1016/0092-8674(79)90186-7. [DOI] [PubMed] [Google Scholar]
  32. Rosen C. A., Haseltine W. A., Lenz J., Ruprecht R., Cloyd M. W. Tissue selectivity of murine leukemia virus infection is determined by long terminal repeat sequences. J Virol. 1985 Sep;55(3):862–866. doi: 10.1128/jvi.55.3.862-866.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Ruddle N. H., Conta B. S., Leinwand L., Kozak C., Ruddle F., Besmer P., Baltimore D. Assignment of the receptor for ecotropic murine leukemia virus to mouse chromosome 5. J Exp Med. 1978 Aug 1;148(2):451–465. doi: 10.1084/jem.148.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ruscetti S., Wolff L. Biological and biochemical differences between variants of spleen focus-forming virus can be localized to a region containing the 3' end of the envelope gene. J Virol. 1985 Dec;56(3):717–722. doi: 10.1128/jvi.56.3.717-722.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ruta M., Bestwick R., Machida C., Kabat D. Loss of leukemogenicity caused by mutations in the membrane glycoprotein structural gene of Friend spleen focus-forming virus. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4704–4708. doi: 10.1073/pnas.80.15.4704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Steeves R. A. Editorial: Spleen focus-forming virus in Friend and Rauscher leukemia virus preparations. J Natl Cancer Inst. 1975 Feb;54(2):289–297. doi: 10.1093/jnci/54.2.289. [DOI] [PubMed] [Google Scholar]
  38. Tambourin P. E., Wendling F., Jasmin C., Smadja-Joffe F. The physiopathology of Friend leukemia. Leuk Res. 1979;3(3):117–129. doi: 10.1016/0145-2126(79)90009-2. [DOI] [PubMed] [Google Scholar]
  39. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Troxler D. H., Ruscetti S. K., Linemeyer D. L., Scolnick E. M. Helper-independent and replication-defective erythroblastosis-inducing viruses contained within anemia-inducing Friend virus complex (FV-A). Virology. 1980 Apr 15;102(1):28–45. doi: 10.1016/0042-6822(80)90067-7. [DOI] [PubMed] [Google Scholar]
  42. Wolff L., Ruscetti S. Malignant transformation of erythroid cells in vivo by introduction of a nonreplicating retrovirus vector. Science. 1985 Jun 28;228(4707):1549–1552. doi: 10.1126/science.2990034. [DOI] [PubMed] [Google Scholar]
  43. Wolff L., Scolnick E., Ruscetti S. Envelope gene of the Friend spleen focus-forming virus: deletion and insertions in 3' gp70/p15E-encoding region have resulted in unique features in the primary structure of its protein product. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4718–4722. doi: 10.1073/pnas.80.15.4718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wolff L., Tambourin P., Ruscetti S. Induction of the autonomous stage of transformation in erythroid cells infected with SFFV: helper virus is not required. Virology. 1986 Jul 15;152(1):272–276. doi: 10.1016/0042-6822(86)90393-4. [DOI] [PubMed] [Google Scholar]

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