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. 1984 Sep;51(3):788–794. doi: 10.1128/jvi.51.3.788-794.1984

The envelope gene and long terminal repeat sequences contribute to the pathogenic phenotype of helper-independent Friend viruses.

A Oliff, K Signorelli, L Collins
PMCID: PMC255845  PMID: 6088801

Abstract

Friend murine leukemia virus (F-MuLV) and Friend mink cell focus-inducing virus (Fr-MCF) are helper-independent murine retroviruses which induce a rapidly fatal erytholeukemia in NIH Swiss mice. Amphotropic clone 4070 (Ampho) is a murine retrovirus which does not cause leukemia in these animals. Mice inoculated with Ampho, an Fr-MCF/Ampho pseudotype, or F-MuLV developed leukemia in 0, 50, and 100% of animals, respectively. To identify the F-MuLV and Fr-MCF sequences responsible for leukemia, we constructed hybrid viral genomes between these viruses and Ampho, using subgenomic fragments of molecularly cloned viral DNA. Transfection of these hybrid viral DNAs into fibroblasts produces recombinant retroviruses. These new viruses are assayed in vivo for their ability to cause leukemia. Recombinant viruses constructed between the Ampho genome and the Fr-MCF envelope gene do not cause leukemia. Similarly, viruses constructed by using either the Fr-MCF long terminal repeat U3 region or the F-MuLV long terminal repeat U3 region and the remainder of the Ampho genome do not cause leukemia. However, if the Fr-MCF envelope gene plus the Fr-MCF U3 region are joined to Ampho, the resulting virus causes erythroleukemia in 14% of mice. Recombinant viruses made between the Fr-MCF envelope gene, the F-MuLV U3 region, and the remainder of the Ampho genome cause erythroleukemia in 38% of mice. This study demonstrates that both the envelope gene of Fr-MCF and the U3 regions of Fr-MCF and F-MuLV contain sequences which contribute to the leukemic phenotype of helper-independent Friend viruses.

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Selected References

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  1. Anand R., Lilly F., Ruscetti S. Viral protein expression in producer and nonproducer clones of friend erythroleukemia cell lines. J Virol. 1981 Feb;37(2):654–660. doi: 10.1128/jvi.37.2.654-660.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chang E. H., Ellis R. W., Scolnick E. M., Lowy D. R. Transformation by cloned Harvey murine sarcoma virus DNA: efficiency increased by long terminal repeat DNA. Science. 1980 Dec 12;210(4475):1249–1251. doi: 10.1126/science.6254153. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Chattopadhyay S. K., Oliff A. I., Linemeyer D. L., Lander M. R., Lowy D. R. Genomes of murine leukemia viruses isolated from wild mice. J Virol. 1981 Sep;39(3):777–791. doi: 10.1128/jvi.39.3.777-791.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. DesGroseillers L., Villemur R., Jolicoeur P. The high leukemogenic potential of Gross passage A murine leukemia virus maps in the region of the genome corresponding to the long terminal repeat and to the 3' end of env. J Virol. 1983 Jul;47(1):24–32. doi: 10.1128/jvi.47.1.24-32.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Even J., Anderson S. J., Hampe A., Galibert F., Lowy D., Khoury G., Sherr C. J. Mutant feline sarcoma proviruses containing the viral oncogene (v-fes) and either feline or murine control elements. J Virol. 1983 Mar;45(3):1004–1016. doi: 10.1128/jvi.45.3.1004-1016.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gonda M. A., Kaminchick J., Oliff A., Menke J., Nagashima K., Scolnick E. M. Heteroduplex analysis of molecular clones of the pathogenic Friend virus complex: Friend murine leukemia virus, Friend mink cell focus-forming virus, and the polycythemia- and anemia-inducing strains of Friend spleen focus-forming virus. J Virol. 1984 Aug;51(2):306–314. doi: 10.1128/jvi.51.2.306-314.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Hartley J. W., Rowe W. P. Naturally occurring murine leukemia viruses in wild mice: characterization of a new "amphotropic" class. J Virol. 1976 Jul;19(1):19–25. doi: 10.1128/jvi.19.1.19-25.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Koch W., Zimmermann W., Oliff A., Friedrich R. Molecular analysis of the envelope gene and long terminal repeat of Friend mink cell focus-inducing virus: implications for the functions of these sequences. J Virol. 1984 Mar;49(3):828–840. doi: 10.1128/jvi.49.3.828-840.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laimins L. A., Gruss P., Pozzatti R., Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. doi: 10.1128/jvi.49.1.183-189.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Neel B. G., Hayward W. S., Robinson H. L., Fang J., Astrin S. M. Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion. Cell. 1981 Feb;23(2):323–334. doi: 10.1016/0092-8674(81)90128-8. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Oliff A., Collins L., Mirenda C. Molecular cloning of Friend mink cell focus-inducing virus: identification of mink cell focus-inducing virus-like messages in normal and transformed cells. J Virol. 1983 Nov;48(2):542–546. doi: 10.1128/jvi.48.2.542-546.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Oliff A., Ruscetti S. A 2.4-kilobase-pair fragment of the Friend murine leukemia virus genome contains the sequences responsible for friend murine leukemia virus-induced erythroleukemia. J Virol. 1983 Jun;46(3):718–725. doi: 10.1128/jvi.46.3.718-725.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oliff A., Ruscetti S., Douglass E. C., Scolnick E. Isolation of transplantable erythroleukemia cells from mice infected with helper-independent Friend murine leukemia virus. Blood. 1981 Aug;58(2):244–254. [PubMed] [Google Scholar]
  25. Pedersen F. S., Crowther R. L., Tenney D. Y., Reimold A. M., Haseltine W. A. Novel leukaemogenic retroviruses isolated from cell line derived from spontaneous AKR tumour. Nature. 1981 Jul 9;292(5819):167–170. doi: 10.1038/292167a0. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Ruscetti S. K., Linemeyer D., Feild J., Troxler D., Scolnick E. M. Characterization of a protein found in cells infected with the spleen focus-forming virus that shares immunological cross-reactivity with the gp70 found in mink cell focus-inducing virus particles. J Virol. 1979 Jun;30(3):787–798. doi: 10.1128/jvi.30.3.787-798.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ruscetti S., Davis L., Feild J., Oliff A. Friend murine leukemia virus-induced leukemia is associated with the formation of mink cell focus-inducing viruses and is blocked in mice expressing endogenous mink cell focus-inducing xenotropic viral envelope genes. J Exp Med. 1981 Sep 1;154(3):907–920. doi: 10.1084/jem.154.3.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Scolnick E., Rands E., Aaronson S. A., Todaro G. J. RNA-dependent DNA polymerase activity in five RNA viruses: divalent cation requirements. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1789–1796. doi: 10.1073/pnas.67.4.1789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Troxler D. H., Scolnick E. M. Rapid leukemia induced by cloned friend strain of replicating murine type-C virus. Association with induction of xenotropic-related RNA sequences contained in spleen focus-forming virus. Virology. 1978 Mar;85(1):17–27. doi: 10.1016/0042-6822(78)90408-7. [DOI] [PubMed] [Google Scholar]
  32. Troxler D. H., Yuan E., Linemeyer D., Ruscetti S., Scolnick E. M. Helper-independent mink cell focus-inducing strains of Friend murine type-C virus: potential relationship to the origin of replication-defective spleen focus-forming virus. J Exp Med. 1978 Sep 1;148(3):639–653. doi: 10.1084/jem.148.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]

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