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. 1972 Oct 1;136(4):832–850. doi: 10.1084/jem.136.4.832

A CLASSIFICATION OF THE MURINE LEUKEMIA VIRUSES

NEUTRALIZATION OF PSEUDOTYPES OF FRIEND SPLEEN FOCUS-FORMING VIRUS BY TYPE-SPECIFIC MURINE ANTISERA

Robert J Eckner 1, Richard A Steeves 1
PMCID: PMC2139277  PMID: 4341440

Abstract

Coinfection of neonatal BALB/c mice with helper-dependent Friend spleen focus-forming virus (SFFV), as contained in the Friend virus (FV) complex, and antigenically distinct Moloney leukemia virus (MolLV) resulted in the recovery of a MolLV pseudotype of SFFV, abbreviated SFFV(MolLV). The antigenic alteration of SFFV was observed by following its neutralization kinetics in vitro by specific Friend or Moloney typing antiserum. Effective pseudotype production was accomplished only when N-tropic LLV-F (the natural helper virus in the FV complex) was inhibited in B-type mice coinfected with an NB-tropic MolLV or other murine leukemia virus (MuLV) preparation. SFFV pseudotypes could not be prepared by using murine viruses other than leukemia viruses. SFFV prepared after two serial passages in the presence of MolLV was effectively neutralized by Moloney antiserum, but not by Friend typing antiserum; therefore, the envelope of the pseudotype virus, SFFV(MolLV), is homogeneous. Pseudotype virus was antigenically stable in the absence of continued mixed infection of BALB/c mice with SFFV(MolLV) and MolLV. However, SFFV(MolLV) was easily converted back to the LLV-F type after only one passage in BALB/c mice coinfected with NB-tropic LLV-F. The antigenic interconversion between LLV-F and MolLV types demonstrated that SFFV is defective with respect to the expression of neutralizable envelope antigens. Analysis of the neutralizable envelope antigens of nine SFFV(MuLV) pseudotypes by a panel of seven typing antisera made possible a "type-specific" SFFV(MuLV) envelope classification. Two major categories have been identified which correspond to the Gross (G) and Friend-Moloney-Rauscher (FMR) subgroups. Further, the FMR subgroup was divided into four types on the basis of distinct neutralization patterns. These results indicated that the specificity observed by cytotoxic G vs. FMR antisera is different from that observed by neutralization kinetics. We therefore suggest that the specific antigens revealed by virus neutralization tests be referred to as type specific.

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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. Aoki T., Boyse E. A., Old L. J., De Harven E., Hämmerling U., Wood H. A. G (Gross) and H-2 cell-surface antigens: location on Gross leukemia cells by electron microscopy with visually labeled antibody. Proc Natl Acad Sci U S A. 1970 Mar;65(3):569–576. doi: 10.1073/pnas.65.3.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BUFFETT R. F., GRACE J. T., Jr, MIRAND E. A. PROPERTIES OF A LYMPHOCYTIC LEUKEMIA AGENT ISOLATED FROM HA/ICR SWISS MICE. Proc Soc Exp Biol Med. 1964 Jun;116:293–297. doi: 10.3181/00379727-116-29230. [DOI] [PubMed] [Google Scholar]
  4. Breyere E. J., Moloney J. B., Jordan W. P. Biological studies on a leukemia virus extracted from C3H plasma cell tumor 70429. J Natl Cancer Inst. 1966 Nov;37(5):699–706. [PubMed] [Google Scholar]
  5. Carter R. L., Chesterman F. C., Rowson K. E., Salaman M. H., Wedderburn N. Induction of lymphoma in BALB-c mice by Rowson-Parr virus (RPV). Int J Cancer. 1970 Sep 15;6(2):290–303. doi: 10.1002/ijc.2910060217. [DOI] [PubMed] [Google Scholar]
  6. DALTON A. J., LAW L. W., MOLONEY J. B., MANAKER R. A. An electron microscopic study of a series of murine lymphoid neoplasms. J Natl Cancer Inst. 1961 Oct;27:747–791. [PubMed] [Google Scholar]
  7. Eckner B. J., Steeves R. A. Defective Friend spleen focus-forming virus: pseudotype neutralization by helper-specific antisera. Nat New Biol. 1971 Feb 24;229(8):241–243. doi: 10.1038/newbio229241a0. [DOI] [PubMed] [Google Scholar]
  8. FIORE-DONATI L., CHIECO-BIANCHI L. INFLUENCE OF HOST FACTORS ON DEVELOPMENT AND TYPE OF LEUKEMIA INDUCED IN MICE BY GRAFFI VIRUS. J Natl Cancer Inst. 1964 May;32:1083–1107. [PubMed] [Google Scholar]
  9. 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]
  10. Fieldsteel A. H., Dawson P. J., Kurahara C. In vivo and in vitro recovery of defective Friend virus by various leukemia viruses. Int J Cancer. 1971 Sep 15;8(2):304–309. doi: 10.1002/ijc.2910080216. [DOI] [PubMed] [Google Scholar]
  11. Fieldsteel A. H., Kurahara C. Moloney leukaemia virus as a helper in retrieving Friend virus from a non-infectious reticulum cell sarcoma. Nature. 1969 Sep 20;223(5212):1274–1274. doi: 10.1038/2231274a0. [DOI] [PubMed] [Google Scholar]
  12. GRAFFI A. Chloroleukemia of mice. Ann N Y Acad Sci. 1957 Oct 21;68(2):540–558. doi: 10.1111/j.1749-6632.1957.tb56107.x. [DOI] [PubMed] [Google Scholar]
  13. GROSS L. Development and serial cellfree passage of a highly potent strain of mouse leukemia virus. Proc Soc Exp Biol Med. 1957 Apr;94(4):767–771. doi: 10.3181/00379727-94-23080. [DOI] [PubMed] [Google Scholar]
  14. Geering G., Old L. J., Boyse E. A. Antigens of leukemias induced by naturally occurring murine leukemia virus: their relation to the antigens of gross virus and other murine leukemia viruses. J Exp Med. 1966 Oct 1;124(4):753–772. doi: 10.1084/jem.124.4.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gregoriades A., Old L. J. Isolation and some characteristics of a group-specific antigen of the murine leukemia viruses. Virology. 1969 Feb;37(2):189–202. doi: 10.1016/0042-6822(69)90198-6. [DOI] [PubMed] [Google Scholar]
  16. HANAFUSA H., HANAFUSA T., RUBIN H. ANALYSIS OF THE DEFECTIVENESS OF ROUS SARCOMA VIRUS, II. SPECIFICATION OF RSV ANTIGENICITY BY HELPER VIRUS. Proc Natl Acad Sci U S A. 1964 Jan;51:41–48. doi: 10.1073/pnas.51.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Huebner R. J. The murine leukemia-sarcoma virus complex. Proc Natl Acad Sci U S A. 1967 Sep;58(3):835–842. doi: 10.1073/pnas.58.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Levy J. P., Varet B., Oppenheim E., Leclerc J. C. Neutralization of Graffi leukaemia virus. Nature. 1969 Nov 8;224(5219):606–608. doi: 10.1038/224606a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. MOLOMUT N., PADNOS M., SMITH L. W. A LYMPHOCYTOPENIC FILTERABLE AGENT DERIVED FROM TISSUE CELL CULTURES OF MURINE CARCINOMA. J Natl Cancer Inst. 1965 Mar;34:403–413. [PubMed] [Google Scholar]
  22. MOLONEY J. B. Biological studies on a lymphoid-leukemia virus extracted from sarcoma 37. I. Origin and introductory investigations. J Natl Cancer Inst. 1960 Apr;24:933–951. [PubMed] [Google Scholar]
  23. 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]
  24. O'Connor T. E., Rauscher F. J., De-Thé G., Fink M. A., Gerber P. Murine leukemia viruses: rupture with ether and detergents to subviral constituents. Natl Cancer Inst Monogr. 1966 Sep;22:205–221. [PubMed] [Google Scholar]
  25. OLD L. J., BOYSE E. A., STOCKERT E. TYPING OF MOUSE LEUKAEMIAS BY SEROLOGICAL METHODS. Nature. 1964 Feb 22;201:777–779. doi: 10.1038/201777a0. [DOI] [PubMed] [Google Scholar]
  26. Pasternak G. Differentiation between viral and new cellular antigens in Graffi leukaemia of mice. Nature. 1967 Jun 24;214(5095):1364–1365. doi: 10.1038/2141364a0. [DOI] [PubMed] [Google Scholar]
  27. Pincus T., Rowe W. P., Lilly F. A major genetic locus affecting resistance to infection with murine leukemia viruses. II. Apparent identity to a major locus described for resistance to friend murine leukemia virus. J Exp Med. 1971 Jun 1;133(6):1234–1241. doi: 10.1084/jem.133.6.1234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. RAUSCHER F. J. A virus-induced disease of mice characterized by erythrocytopoiesis and lymphoid leukemia. J Natl Cancer Inst. 1962 Sep;29:515–543. [PubMed] [Google Scholar]
  29. Rich M. A., Geldner J., Meyers P. Studies on murine leukemia. J Natl Cancer Inst. 1965 Sep;35(3):523–536. doi: 10.1093/jnci/35.3.523. [DOI] [PubMed] [Google Scholar]
  30. Rowe W. P., Murphy F. A., Bergold G. H., Casals J., Hotchin J., Johnson K. M., Lehmann-Grube F., Mims C. A., Traub E., Webb P. A. Arenoviruses: proposed name for a newly defined virus group. J Virol. 1970 May;5(5):651–652. doi: 10.1128/jvi.5.5.651-652.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Rowson K. E., Parr I. B. A new virus of minimal pathogenicity associated with Friend virus. I. Isolation by end-point dilution. Int J Cancer. 1970 Jan 15;5(1):96–102. doi: 10.1002/ijc.2910050113. [DOI] [PubMed] [Google Scholar]
  33. Steeves R. A., Axelrad A. A. Neutralization kinetics of friend and Rauscher leukemia viruses studied with the spleen focus assay method. Int J Cancer. 1967 May 15;2(3):235–244. doi: 10.1002/ijc.2910020306. [DOI] [PubMed] [Google Scholar]
  34. Steeves R. A. Cellular antigen of Friend virus-induced leukemias. Cancer Res. 1968 Feb;28(2):338–342. [PubMed] [Google Scholar]
  35. 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]
  36. Steeves R. A., Eckner R. J. Host-induced changes in infectivity of Friend spleen focus-forming virus. J Natl Cancer Inst. 1970 Mar;44(3):587–594. [PubMed] [Google Scholar]
  37. Steeves R. A., Eckner R. J., Mirand E. A., Priore R. L. Rapid assay of murine leukemia virus helper activity for Friend spleen focus-forming virus. J Natl Cancer Inst. 1971 Jun;46(6):1219–1228. [PubMed] [Google Scholar]
  38. Steeves R. A., Fjelde A., Mirand E. A. Helper activity of human leukemic tissue extracts for leukemia virus expression in mice. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2391–2395. doi: 10.1073/pnas.68.10.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stim T. B. Interference of Cocal virus with Friend leukemia virus-induced splenomegaly in DBA-2J mice. Proc Soc Exp Biol Med. 1970 Jun;134(2):413–420. doi: 10.3181/00379727-134-34803. [DOI] [PubMed] [Google Scholar]
  40. Traub E. A FILTERABLE VIRUS RECOVERED FROM WHITE MICE. Science. 1935 Mar 22;81(2099):298–299. doi: 10.1126/science.81.2099.298. [DOI] [PubMed] [Google Scholar]
  41. Vogt P. K. Envelope classification of avian RNA tumor viruses. Bibl Haematol. 1970;(36):153–167. doi: 10.1159/000391704. [DOI] [PubMed] [Google Scholar]
  42. Vogt P. K. Genetically stable reassortment of markers during mixed infection with avian tumor viruses. Virology. 1971 Dec;46(3):947–952. doi: 10.1016/0042-6822(71)90093-6. [DOI] [PubMed] [Google Scholar]
  43. Wheelock E. F. Inhibitory effects of Sendai virus on Friend virus leukemia in mice. J Natl Cancer Inst. 1967 May;38(5):771–778. [PubMed] [Google Scholar]

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