Intracellular and Systemic Regulation of Biologically Distinguishable Endogenous Type C RNA Viruses of Mouse Cells

  • Stuart A. Aaronson
  • John R. Stephenson
Part of the Contemporary Topics in Immunobiology book series (CTI, volume 6)


The inherited basis for factors involved in leukemogenesis in mice was established many years ago with the development of inbred strains having extremely high susceptibility to the natural occurrence of leukemia (Furth et al., 1933; MacDowell and Richter, 1935). The first evidence that viruses were etiologically involved in this disease was provided by Gross (1951), who demonstrated transmission of leukemia to mice by filtrates from tumors of high-leukemia-incidence strains. Subsequent studies in vivo have confirmed and extended these observations, documenting the intimate association of type C RNA viruses with the mouse and the etiological role of the virus in leukemia.


Mouse Cell Murine Leukemia Virus Embryo Cell Virus Release Endogenous Virus 


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  1. Aaronson, S. A., 1971, Chemical activation of focus-forming virus from nonproducer cells transformed by murine sarcoma virus, Proc. Natl Acad. Sci. U.S.A. 68: 3069.PubMedCrossRefGoogle Scholar
  2. Aaronson, S. A., and Dunn, C. Y., 1974a, Endogenous C-type viruses of BALB/c cells: Frequencies of spontaneous and chemical induction, J. Virol. 13: 181.PubMedGoogle Scholar
  3. Aaronson, S. A., and Dunn, C. Y., 1974b, High frequency C-type virus induction by inhibitors of protein synthesis, Science 183: 422.PubMedCrossRefGoogle Scholar
  4. Aaronson, S. A., and Stephenson, J. R., 1973, Independent segregation of loci for activation of biologically distinguishable RNA C-type viruses in mouse cells, Proc. Natl. Acad. Sci. U.S.A. 70: 2055.PubMedCrossRefGoogle Scholar
  5. Aaronson, S. A., and Stephenson, J. R., 1974, Widespread natural occurrence of high-titered neutralizing antibodies to a specific class of endogenous mouse C-type virus. Proc. Natl. Acad. Sci. U.S.A. 71: 1957.PubMedCrossRefGoogle Scholar
  6. Aaronson, S. A., and Stephenson, J. R., 1975, Differential cellular regulation of three distinct classes of type-C RNA viruses endogenous to mouse cells, Cold Spring Harbor Symp. Quant. Biol. 39: 1129.PubMedCrossRefGoogle Scholar
  7. Aaronson, S. A., and Weaver, C. A., 1971, Characterization of murine sarcoma virus (Kirsten) transformation of mouse and human cells, J. Gen. Virol. 13: 245.PubMedCrossRefGoogle Scholar
  8. Aaronson, S. A., Hartley, J. W., and Todaro, G. J., 1969, Mouse leukemia virus: “Spontaneous” release by mouse embryo cells after long-term in vitro cultivation, Proc. Natl Acad. Sci. U.S.A. 64: 87.PubMedCrossRefGoogle Scholar
  9. Aaronson, S. A., Todaro, G. J., and Scolnick, E. M., 1971, Induction of C-type viruses from clonal lines of virus-free BALB/3T3 cells, Science 174: 157.PubMedCrossRefGoogle Scholar
  10. Aaronson, S. A., Anderson, G. R., Dunn, C. Y., and Robbins, K. C., 1974a, Cycloheximide induction of type-C RNA virus: Increased expression of virus-specific RNA, Proc. Natl. Acad. Sci U.S.A. 71: 3941.PubMedCrossRefGoogle Scholar
  11. Aaronson, S. A., Stephenson, J. R., and Greenberger, J. S., 1914b, Cellular replication and persistence of inducible RNA type C viruses, J. Virol. 13: 1404.Google Scholar
  12. Axelrad, A., 1966, Genetic control of susceptibility to Friend leukemia virus in mice: Studies with the spleen focus assay method, Natl. Cancer Inst. Monogr. 22: 619.PubMedGoogle Scholar
  13. Benveniste, R. E., and Todaro, G. J., 1974, Evolution of C-type viral genes: Inheritance of exogenously acquired viral genes, Nature (London) 252: 456.CrossRefGoogle Scholar
  14. Benveniste, R. E., Lieber, M. M., and Todaro, G. J., 1974, A distinct class of inducible murine type-C virus that replicates in the rabbit SIRC cell line, Proc. Natl. Acad. Sci. U.S.A. 71: 602.PubMedCrossRefGoogle Scholar
  15. Chattopadhyay, S. K., Lowy, D. R., Teich, N. M., Levine, A. S., and Rowe, W. P., 1974, Evidence that the AKR murine-leukemia-virus genome is complete in DNA of the high-virus AKR mouse and incomplete in the DNA of the “virus-negative” NIH mouse, Proc. Natl. Acad. Sci U.S.A. 71: 167.PubMedCrossRefGoogle Scholar
  16. Dunn, C. Y., Aaronson, S. A., and Stephenson, J. R., 1975, Interactions of chemical inducers and steroid enhancers of endogenous mouse type C RNA viruses, Virology 66: 579.PubMedCrossRefGoogle Scholar
  17. Eckner, R. J., 1973, Helper-dependent properties of Friend spleen focus-forming virus: Effect of the Fv-1 gene on the late steps of virus synthesis, J. Virol. 12: 523.PubMedGoogle Scholar
  18. Furth, J., Seibold, H. R., and Rathbone, R. R., 1933, Experimental studies on lymphomatosis of mice, Am. J. Cancer 19: 521.Google Scholar
  19. Gelb, L. D., Aaronson, S. A., and Martin, M. A., 1971, Heterogeneity of murine leukemia virus in vitro DNA; detection of viral DNA in mammalian cells, Science 172: 1354.CrossRefGoogle Scholar
  20. Gelb, L. D., Milstien, J. B., Martin, M. A., and Aaronson, S. A., 1973, Characterization of murine leukemia virus-specific DNA present in normal mouse cells, Nature (London) New Biol 244: 76.Google Scholar
  21. Greenberger, J. S., and Aaronson, S. A., 1973, In vivo inoculation of RNA C-type viruses inducing regression of experimental solid tumors, J. Natl. Cancer Inst. 51: 1935.PubMedGoogle Scholar
  22. Greenberger, J. S., Phillips, S. M., Stephenson, J. R., and Aaronson, S. A., 1975a, Induction of mouse type-C RNA virus by lipopolysaccharides and concanavalin A, J. Immunol. 115: 317.PubMedGoogle Scholar
  23. Greenberger, J. S., Stephenson, J. R., Moloney, W. C., and Aaronson, S. A., 1975b, Different hematoligic diseases induced by type-C viruses chemically activated from embryo cells of different mouse strains, Cancer Res. 35: 245.PubMedGoogle Scholar
  24. Gross, L., 1951, Pathogenic properties, and “vertical” transmission of the mouse leukemia agent, Proc. Soc. Exp. Biol Med. 78: 342.PubMedGoogle Scholar
  25. Hino, S., Stephenson, J. R., and Aaronson, S. A., 1976, Radioimmunoassays for the 70,000-molecular-weight glycoproteins of endogenous mouse type-C viruses: Viral antigen expression in normal mouse tissues, J. Virol 18: 933.PubMedGoogle Scholar
  26. Hirsch, M. S., Phillips, S. M., Solnick, C., Black, P. H., Schwartz, R. S., and Carpenter, C. B., 1972, Activation of leukemia viruses by graft-versus-host and mixed lymphocyte reactions in vitro, Proc. Natl Acad. Sci. U.S.A. 69: 1069.PubMedCrossRefGoogle Scholar
  27. Huang, A. S., Besmer, P., Chu, L., and Baltimore, D., 1973, Growth of pseudotypes of vesicular stomatitis virus with N-tropic murine leukemia virus coats in cells resistant to N-tropic viruses, J. Virol 12: 659.PubMedGoogle Scholar
  28. Huebner, R. J., Kelloff, G. J., Sarma, P. S., Lane, W. T., and Turner, H. C., 1970, Group-specific antigen expression during embryogenesis of the genome of the C-type RNA tumor virus: Implications for ontogenesis and oncogenesis, Proc. Natl. Acad. Sci U.S.A. 67: 366.PubMedCrossRefGoogle Scholar
  29. Ihle, J. N., Yurconic, M., Jr., and Hanna, M. G., Jr., 1973, Autogenous immunity to endogenous RNA tumor virus: Radioimmune precipitation assay of mouse serum antibody levels, J. Exp. Med. 138: 194.PubMedCrossRefGoogle Scholar
  30. Ihle, J. N., Hanna, M. G., Jr., Roberson, L. E., and Kenney, F. T., 1974, Autogenous immunity to endogenous RNA tumor virus: Identification of antibody reactive to select viral antigens, J. Exp. Med, 139: 1568.PubMedCrossRefGoogle Scholar
  31. Klement, V., Nicolson, M. O., and Huebner, R. J., 1971, Rescue of the genome of focus-forming virus from rat nonproductive lines by 5′-bromodeoxyuridine, Nature (London) New Biol. 234: 12.Google Scholar
  32. Krontiris, T., Soeiro, R., and Fields, B. N., 1973, Host range restriction of Friend leukemia virus. Role of the viral outer coat, Proc. Natl Acad. Sci. U.S.A. 70: 2549.PubMedCrossRefGoogle Scholar
  33. Lee, J. C., Hanna, M. G., Jr., Ihle, J. N., and Aaronson, S. A., 1974, Autogenous immunity to endogenous RNA tumor virus: Differential reactivities of immunoglobulins M and G to virus envelope antigens, J. Virol. 14: 773.PubMedGoogle Scholar
  34. Lieber, M. M., Sherr, C. J., and Todaro, G. J., 1974, S-tropic murine type-C viruses: Frequency of isolation from continuous cell lines, leukemia virus preparations and normal spleens, Int. J. Cancer 13: 587.PubMedCrossRefGoogle Scholar
  35. Lilly, F., Duran-Reynals, M. L., and Rowe, W. P., 1975, Correlation of early leukemia virus titer and H-2 type with spontaneous leukemia of the BALB/c x AKR cross: A genetic analysis, J. Exp. Med. 141: 882.PubMedGoogle Scholar
  36. Levy, J. A., 1973, Xenotropic viruses: Murine leukemia viruses associated with NIH Swiss, NZB, and other mouse strains, Science 182: 1151.PubMedCrossRefGoogle Scholar
  37. Levy, J. A., and Pincus, T., 1970, Demonstration of biological activity of a murine leukemia virus of New Zealand Black mice, Science 170: 326.PubMedCrossRefGoogle Scholar
  38. Lowy, D. R., Rowe, W. P., Teich, N., and Hartley, J. W., 1971, Murine leukemia virus: High-frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine, Science 174: 155.PubMedCrossRefGoogle Scholar
  39. MacDowell, E. C., and Richter, M. N., 1935, Mouse leukemia, IX. The role of heredity in spontaneous cases, Arch. Pathol. 20: 709.Google Scholar
  40. Meier, H., Taylor, B. A., Cherry, M., and Huebner, R. J., 1973, Host-gene control of type-C RNA tumor virus expression and tumorigenesis in inbred mice, Proc. Natl Acad. Sci. U.S.A. 70: 1450.PubMedCrossRefGoogle Scholar
  41. Mellors, R. C., Aoki, T., and Huebner, R. J., 1969. Further implication of murine leukemia-like virus in the disorders of NZB mice, J. Exp. Med. 129: 1045.PubMedCrossRefGoogle Scholar
  42. Moroni, C., Schumann, G., Robert-Guroff, M., Suter, E. R., and Martin, D., 1975, Induction of endogenous murine C-type virus in spleen cell cultures treated with mitogens and 5-bromo-2′-deoxyuridine, Proc. Natl Acad. Sci. U.S.A. 72: 535.PubMedCrossRefGoogle Scholar
  43. Odaka, T., and Yamamoto, T., 1962, Inheritance of susceptibility to Friend mouse leukemia virus, Jpn. J. Exp. Med. 32: 405.PubMedGoogle Scholar
  44. Oldstone, M. B., Aoki, T., and Dixon, F. J., 1972, The antibody response of mice to murine leukemia virus in spontaneous infection: Absence of classical immunological tolerance, Proc. Natl Acad. Sci. U.S.A. 69: 134.PubMedCrossRefGoogle Scholar
  45. Pincus, T., Rowe, W. P., and Lilly, F., 1971, 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. 133: 1234.PubMedCrossRefGoogle Scholar
  46. Rowe, W. P., 1972, Studies of genetic transmission of murine leukemia virus by AKR mice. I. Crosses with Fv-ln strains of mice, J. Exp. Med. 136: 1272.PubMedCrossRefGoogle Scholar
  47. Rowe, W. P., Hartley, J. W., and Bremner, T., 1972, Genetic mapping of a murine leukemia virus-inducing locus of AKR mice, Science 178: 860.PubMedCrossRefGoogle Scholar
  48. Sherr, C. J., Lieber, M. M., and Todaro, G. J., 1974, Mixed splenocyte cultures and graft-versus-host reactions selectively induce an “S-tropic” murine type C virus, Cell 1: 55.CrossRefGoogle Scholar
  49. Strand, M., and August, J. T., 1973, Structural proteins of oncogenic ribonucleic acid viruses: Interspec II, a new interspecies antigen, J. Biol Chem. 248: 5627.PubMedGoogle Scholar
  50. Stephenson, J. R., and Aaronson, S. A., 1972c, Genetic factors influencing C-type RNA virus induction, J. Exp. Med. 136: 175.PubMedCrossRefGoogle Scholar
  51. Stephenson, J. R., and Aaronson, S. A., 1912b, A genetic locus for inducibility of C-type virus in BALB/c cells: The effect of a nonlinked regulatory gene on detection of virus after chemical activation, Proc. Natl. Acad. Sci. U.S.A. 69: 2798.CrossRefGoogle Scholar
  52. Stephenson, J. R., and Aaronson, S. A., 1972c, Antigenic properties of murine sarcoma virus-transformed BALB/3T3 nonproducer cells, J. Exp. Med. 135: 503.PubMedCrossRefGoogle Scholar
  53. Stephenson, J. R., and Aaronson, S. A., 1973a, Expression of endogenous RNA C-type virus group specific antigens in mammalian cells, J. Virol. 12: 564.PubMedGoogle Scholar
  54. Stephenson, J. R., and Aaronson, S. A., 1973b, Segregation of genetic loci for virus inducibility in high and low leukemia incidence strains of mice, Science 180: 865.PubMedCrossRefGoogle Scholar
  55. Stephenson, J. R., and Aaronson, S. A., 1974, Demonstration of a genetic factor influencing spontaneous release of a xenotropic virus of mouse cells, Proc. Natl. Acad. Sci. U.S.A. 71: 4925.PubMedCrossRefGoogle Scholar
  56. Stephenson, J. R., Aaronson, S. A., Arnstein, P., Huebner, R. J., and Tronick, S. R., 1974a, Demonstration of two immunologically distinct xenotropic RNA type-C viruses of mouse cells, Virology 61: 244.Google Scholar
  57. Stephenson, J. R., Crow, J. D., and Aaronson, S. A., 1974b, Differential activation of biologically distinguishable endogenous mouse type-C RNA viruses: Interaction with host cell regulatory factors, Virology 61: 411.PubMedCrossRefGoogle Scholar
  58. Stephenson, J. R., Greenberger, J. S., and Aaronson, S. A., 1974c, Oncogenicity of an endogenous C-type virus chemically activated from mouse cells in culture, J. Virol. 13: 237.PubMedGoogle Scholar
  59. Stephenson, J. R., Tronick, S. R., and Aaronson, S. A., 1974d, Isolation from BALB/c mouse cells of a structural polypeptide of a third endogenous type-C virus, Cell 3: 347.PubMedCrossRefGoogle Scholar
  60. Stephenson, J. R., Tronick, S. R., and Aaronson, S. A., 1974c, Analysis of type specific antigenic determinants of two structural polypeptides of mouse RNA C-type viruses, Virology 58: 1.PubMedCrossRefGoogle Scholar
  61. Stephenson, J. R., Tronick, S. R., Reynolds, R. K., and Aaronson, S. A., 1974f, Isolation and characterization of C-type viral gene products of virus negative mouse cells, J. Exp. Med. 139: 427.PubMedCrossRefGoogle Scholar
  62. Stephenson, J. R., Reynolds, R. K., Tronick, S. R., and Aaronson, S. A., 1975, Distribution of three classes of endogenous type-C RNA viruses among inbred strains of mice, Virology 67: 404.CrossRefGoogle Scholar
  63. Taylor, B. A., Meier, H., and Myers, D. D., 1971, Host-gene control of C-type RNA tumor virus: Inheritance of the group specific antigen of murine leukemia virus, Proc. Natl Acad. Sci. U.S.A. 68: 3190.PubMedCrossRefGoogle Scholar
  64. Todaro, G. J., Arnstein, P., Parks, W. P., Lennette, E. H., and Huebner, R. J., 1973, A type-C virus in human rhabdomyosarcoma cells after inoculation into NIH Swiss mice treated with antithymocyte serum, Proc. Natl Acad. Sci. U.S.A. 70: 859.PubMedCrossRefGoogle Scholar
  65. Tronick, S. R., Stephenson, J. R., and Aaronson, S. A., 1974, Comparative immunologic studies of primate RNA C-type viruses: Radioimmunoassay for a low molecular weight polypeptide of woolly monkey leukemia virus, Virology 57: 347.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Stuart A. Aaronson
    • 1
  • John R. Stephenson
    • 1
  1. 1.Laboratory of RNA Tumor Viruses, Viral Carcinogenesis BranchNational Cancer InstituteBethesdaUSA

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