Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Aug;84(16):5893–5897. doi: 10.1073/pnas.84.16.5893

Role of antibodies to murine leukemia virus p15E transmembrane protein in immunotherapy against AKR leukemia: a model for studies in human acquired immunodeficiency syndrome.

H J Thiel, H Schwarz, P Fischinger, D Bolognesi, W Schäfer
PMCID: PMC298969  PMID: 3039513

Abstract

Previous studies have demonstrated that the onset of AKR leukemia could be dramatically delayed and the overall incidence significantly reduced following treatment with high-titered heterologous antibodies directed against the gp71 major glycoprotein of the virus. However, to be maximally successful, the treatment had to be initiated during the postnatal period of the AKR mouse, encompassing a narrow window representing approximately the first 3 days of life. In the present study we sought to extend this barrier by including antibodies directed against a second envelope component of the virion, the transmembrane protein, p15E. We demonstrate that although neither antibodies to gp71 nor antibodies to p15E could influence the course of leukemia development when applied individually later in life, a combination of the two antibodies was effective even if given as late as 5 months after birth. The significance of these studies is discussed in relation to human retrovirus-associated diseases.

Full text

PDF
5893

Images in this article

5894Image
on p.5894

Selected References

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

  1. Bolognesi D. P., Montelaro R. C., Frank H., Schäfer W. Assembly of type C oncornaviruses: a model. Science. 1978 Jan 13;199(4325):183–186. doi: 10.1126/science.202022. [DOI] [PubMed] [Google Scholar]
  2. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  3. Bowen D. L., Lane H. C., Fauci A. S. Immunopathogenesis of the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):704–709. doi: 10.7326/0003-4819-103-5-704. [DOI] [PubMed] [Google Scholar]
  4. Buckheit R. W., Jr, Bolognesi D. P., Weinhold K. J. The effects of leukemosuppressive immunotherapy on bone marrow infectious cell centers in AKR mice. Virology. 1987 Apr;157(2):387–396. doi: 10.1016/0042-6822(87)90281-9. [DOI] [PubMed] [Google Scholar]
  5. Cianciolo G. J., Copeland T. D., Oroszlan S., Snyderman R. Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science. 1985 Oct 25;230(4724):453–455. doi: 10.1126/science.2996136. [DOI] [PubMed] [Google Scholar]
  6. Cianciolo G. J., Phipps D., Snyderman R. Human malignant and mitogen-transformed cells contain retroviral P15E-related antigen. J Exp Med. 1984 Mar 1;159(3):964–969. doi: 10.1084/jem.159.3.964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cloyd M. W. Characterization of target cells for MCF viruses in AKR mice. Cell. 1983 Jan;32(1):217–225. doi: 10.1016/0092-8674(83)90512-3. [DOI] [PubMed] [Google Scholar]
  8. Deinhardt F., Bergholz C., Hunsmann G., Schneider J., Thiel H. J., Beug H., Schäfer W. Studies of simian sarcoma and simian sarcoma-associated virus. I. Analysis of viral structural proteins, and preparation and characterization of antiserum specific for viral envelope components. Z Naturforsch C. 1978 Nov-Dec;33(11-12):969–980. doi: 10.1515/znc-1978-11-1227. [DOI] [PubMed] [Google Scholar]
  9. DesGroseillers L., Jolicoeur P. The tandem direct repeats within the long terminal repeat of murine leukemia viruses are the primary determinant of their leukemogenic potential. J Virol. 1984 Dec;52(3):945–952. doi: 10.1128/jvi.52.3.945-952.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fischinger P. J., Dunlop N. M., Schwarz H., Ihle J. N., Weinhold K., Bolognesi D. P., Schafer W. XVIII. Effective treatment of AKR leukemia with antibody to gp7 1 eliminates the neonatal burst of ecotropic AKR virus producing cells. Virology. 1982 May;119(1):68–81. doi: 10.1016/0042-6822(82)90066-6. [DOI] [PubMed] [Google Scholar]
  11. Fischinger P. J., Sch5AAFER W., Bolognesi D. P. Neutralization of homologous and heterologous oncornaviruses by antisera against the p15(E) and gp71 polypeptides of Friend murine leukemia virus. Virology. 1976 May;71(1):169–184. doi: 10.1016/0042-6822(76)90103-3. [DOI] [PubMed] [Google Scholar]
  12. Fisher A. G., Ratner L., Mitsuya H., Marselle L. M., Harper M. E., Broder S., Gallo R. C., Wong-Staal F. Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects. Science. 1986 Aug 8;233(4764):655–659. doi: 10.1126/science.3014663. [DOI] [PubMed] [Google Scholar]
  13. Fowler A. K., Twardzik D. R., Reed C. D., Weislow O. S., Hellman A. Inhibition of lymphocyte transformation by disrupted murine oncornavirus. Cancer Res. 1977 Dec;37(12):4529–4531. [PubMed] [Google Scholar]
  14. 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]
  15. Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. At least four viral genes contribute to the leukemogenicity of murine retrovirus MCF 247 in AKR mice. J Virol. 1985 Jan;53(1):158–165. doi: 10.1128/jvi.53.1.158-165.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hunsmann G., Claviez M., Moennig V., Schwarz H., Schäfer W. Properties of mouse leukemia viruses. X. Occurrence of viral structural antigens on the cell surface as revealed by a cytotoxicity test. Virology. 1976 Jan;69(1):157–168. doi: 10.1016/0042-6822(76)90203-8. [DOI] [PubMed] [Google Scholar]
  17. Iglehart J. D., Weinhold K. J., Ward E. C., Matthews T. J., Langlois A. J., Schäfer W., Bolognesi D. P. Prospects for the immunological management of lethal tumors. Cancer Invest. 1983;1(5):409–421. doi: 10.3109/07357908309048509. [DOI] [PubMed] [Google Scholar]
  18. Ihle J. N., Jr, Hanna M. G., Schafer W., Hunsmann G., Bolognesi D. P., HUPER G. Polypeptides of mammalian oncornaviruses. III. Localization of p 15 and reactivity with natural antibody. Virology. 1975 Jan;63(1):60–67. doi: 10.1016/0042-6822(75)90370-0. [DOI] [PubMed] [Google Scholar]
  19. Ihle J. N., Yurconic M., Jr, Hanna M. G., Jr Autogenous immunity to endogenous RNA tumor virus. Radioimmune precipitation assay of mouse serum antibody levels. J Exp Med. 1973 Jul 1;138(1):194–208. doi: 10.1084/jem.138.1.194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
  21. 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]
  22. Mathes L. E., Olsen R. G., Hebebrand L. C., Hoover E. A., Schaller J. P., Adams P. W., Nichols W. S. Immunosuppressive properties of a virion polypeptide, a 15,000-dalton protein, from feline leukemia virus. Cancer Res. 1979 Mar;39(3):950–955. [PubMed] [Google Scholar]
  23. Metcalf D., Moulds R. Immune responses in preleukaemic and leukaemic AKR mice. Int J Cancer. 1967 Jan 15;2(1):53–58. doi: 10.1002/ijc.2910020109. [DOI] [PubMed] [Google Scholar]
  24. Price P. J., Bellew T. M., King M. P., Freeman A. E., Gilden R. V., Huebner R. J. Prevention of viral-chemical co-carcinogenesis in vitro by type-specific anti-viral antibody. Proc Natl Acad Sci U S A. 1976 Jan;73(1):152–155. doi: 10.1073/pnas.73.1.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rowe W. P., Pincus T. Quantitative studies of naturally occurring murine leukemia virus infection of AKR mice. J Exp Med. 1972 Feb 1;135(2):429–436. doi: 10.1084/jem.135.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sarngadharan M. G., Popovic M., Bruch L., Schüpbach J., Gallo R. C. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. doi: 10.1126/science.6324345. [DOI] [PubMed] [Google Scholar]
  27. Schafer W., Hunsmann G., Moennig V., Noranha F., Bolognesi D. P., Green R. W., Hüper G. Polypeptides of mammalian oncornaviruses. II Characterization of murine leukemia virus polypeptide (p 15) bearing interspecies reactivity. Virology. 1975 Jan;63(1):48–59. doi: 10.1016/0042-6822(75)90369-4. [DOI] [PubMed] [Google Scholar]
  28. Schwarz H., Fischinger P. J., Ihle J. N., Thiel H. J., Weiland F., Bolognesi D. P., Schäfer W. Properties of mouse leukemia viruses. XVI. Suppression of spontaneous fetal leukemias in AKR mice by treatment with broadly reacting antibody against the viral glycoprotein gp 71. Virology. 1979 Feb;93(1):159–174. doi: 10.1016/0042-6822(79)90284-8. [DOI] [PubMed] [Google Scholar]
  29. Schwarz H., Ihle J. N., Wecker E., Fischinger P. J., Thiel H. J., Bolognesi D. P., Schäfer W. Properties of mouse leukemia viruses. XVII. Factors required for successful treatment of spontaneous AKR leukemia by antibodies against gp71. Virology. 1981 Jun;111(2):568–578. doi: 10.1016/0042-6822(81)90358-5. [DOI] [PubMed] [Google Scholar]
  30. Schwarz H., Thiel H. J., Weinhold K. J., Bolognesi D. P., Schäfer W. Stimulierung der Immunreaktivität gegen endogene Retroviren und Schutz gegen Leukämie bei älteren AKR-Mäusen nach Impfung mit Antikörpern gegen Virusoberflächen-Komponenten. Rolle des Antikörpers gegen p15(E). Z Naturforsch C. 1984 Nov-Dec;39(11-12):1199–1202. [PubMed] [Google Scholar]
  31. Schwarz H., Thiel H. J., Weinhold K., Fischinger P., Bolognesi D., Schäfer W. Properties of mouse leukemia viruses: XX. Variation of AKR Substrains in response to antibody therapy. Virology. 1986 Apr 15;150(1):247–251. doi: 10.1016/0042-6822(86)90283-7. [DOI] [PubMed] [Google Scholar]
  32. Schäfer W. Der Mäuse-Inzuchstamm STU. Entwicklung und Eigenschaften. Z Naturforsch C. 1979 Mar-Apr;34(3-4):306–309. [PubMed] [Google Scholar]
  33. Schäfer W., Schwarz H., Thiel H. J., Wecker E., Bolognesi D. P. Properties of mouse leukemia viruses. XIII. Serum therapy of virus-induced murine leukemias. Virology. 1976 Dec;75(2):401–418. doi: 10.1016/0042-6822(76)90039-8. [DOI] [PubMed] [Google Scholar]
  34. Thiel H. J., Broughton E. M., Matthews T. J., Schäfer W., Bolognesi D. P. Interspecies reactivity of type C and D retrovirus p 15E and p 15C proteins. Virology. 1981 May;111(1):270–274. doi: 10.1016/0042-6822(81)90671-1. [DOI] [PubMed] [Google Scholar]
  35. Weinhold K. J., Hüper G., Matthews T. J., Fischinger P. J., Ihle J. N., Schwarz H., Thiel H. J., Schäfer W., Bolognesi D. P. Properties of mouse leukemia viruses. XIX. Effective antibody therapy of AKR leukemia occurs independently of virus neutralization and produces long-term changes in the virus status of the thymus. Virology. 1984 May;135(1):105–117. doi: 10.1016/0042-6822(84)90121-1. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES