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. 1992 Jul;66(7):4497–4507. doi: 10.1128/jvi.66.7.4497-4507.1992

Protection against Friend retrovirus-induced leukemia by recombinant vaccinia viruses expressing the gag gene.

M Miyazawa 1, J Nishio 1, B Chesebro 1
PMCID: PMC241259  PMID: 1534853

Abstract

High sequence variability in the envelope gene of human immunodeficiency virus has provoked interest in nonenvelope antigens as potential immunogens against retrovirus infection. However, the role of core protein antigens encoded by the gag gene in protective immunity against retroviruses is unclear. By using recombinant vaccinia viruses expressing the Friend murine leukemia helper virus (F-MuLV) gag gene, we could prime CD4+ T-helper cells and protectively immunize susceptible strains of mice against Friend retrovirus infection. Recovery from leukemic splenomegaly developed more slowly after immunization with vaccinia virus-F-MuLV gag than with vaccinia virus-F-MuLV env; however, genetic nonresponders to the envelope protein could be partially protected with Gag vaccines. Class switching of F-MuLV-neutralizing antibodies from immunoglobulin M to immunoglobulin G after challenge with Friend virus complex was facilitated in mice immunized with the Gag antigen. Sequential deletion of the gag gene revealed that the major protective epitope was located on the N-terminal hydrophobic protein p15.

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Selected References

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

  1. Achour A., Picard O., Zagury D., Sarin P. S., Gallo R. C., Naylor P. H., Goldstein A. L. HGP-30, a synthetic analogue of human immunodeficiency virus (HIV) p17, is a target for cytotoxic lymphocytes in HIV-infected individuals. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7045–7049. doi: 10.1073/pnas.87.18.7045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boucher C. A., Krone W. J., Goudsmit J., Meloen R. H., Naylor P. H., Goldstein A. L., Sun D. K., Sarin P. S. Immune response and epitope mapping of a candidate HIV-1 p17 vaccine HGP30. J Clin Lab Anal. 1990;4(1):43–47. doi: 10.1002/jcla.1860040109. [DOI] [PubMed] [Google Scholar]
  3. Britt W. J., Chesebro B., Portis J. L. Identification of a unique erythroleukemia-associated retroviral gp70 expressed during early stages of normal erythroid differentiation. J Exp Med. 1984 Jun 1;159(6):1591–1603. doi: 10.1084/jem.159.6.1591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chakrabarti S., Brechling K., Moss B. Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol. 1985 Dec;5(12):3403–3409. doi: 10.1128/mcb.5.12.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesebro B., Britt W., Evans L., Wehrly K., Nishio J., Cloyd M. Characterization of monoclonal antibodies reactive with murine leukemia viruses: use in analysis of strains of friend MCF and Friend ecotropic murine leukemia virus. Virology. 1983 May;127(1):134–148. doi: 10.1016/0042-6822(83)90378-1. [DOI] [PubMed] [Google Scholar]
  6. Chesebro B., Miyazawa M., Britt W. J. Host genetic control of spontaneous and induced immunity to Friend murine retrovirus infection. Annu Rev Immunol. 1990;8:477–499. doi: 10.1146/annurev.iy.08.040190.002401. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Chesebro B., Wehrly K., Stimpfling J. Host genetic control of recovery from Friend leukemia virus-induced splenomegaly: mapping of a gene within the major histocompatability complex. J Exp Med. 1974 Dec 1;140(6):1457–1467. doi: 10.1084/jem.140.6.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Collins J. K., Britt W. J., Chesebro B. Cytotoxic T lymphocyte recognition of gp70 on Friend virus-induced erythroleukemia cell clones. J Immunol. 1980 Sep;125(3):1318–1324. [PubMed] [Google Scholar]
  10. Collins J. K., Chesebro B. Spontaneous cessation of Friend murine leukemia virus production by leukemia cell line Y57: overgrowth by nonproducer cells. J Natl Cancer Inst. 1980 May;64(5):1153–1159. [PubMed] [Google Scholar]
  11. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  12. Earl P. L., Hügin A. W., Moss B. Removal of cryptic poxvirus transcription termination signals from the human immunodeficiency virus type 1 envelope gene enhances expression and immunogenicity of a recombinant vaccinia virus. J Virol. 1990 May;64(5):2448–2451. doi: 10.1128/jvi.64.5.2448-2451.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science. 1986 Nov 7;234(4777):728–731. doi: 10.1126/science.3490689. [DOI] [PubMed] [Google Scholar]
  14. Ertl H. C., Dietzschold B., Gore M., Otvos L., Jr, Larson J. K., Wunner W. H., Koprowski H. Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein. J Virol. 1989 Jul;63(7):2885–2892. doi: 10.1128/jvi.63.7.2885-2892.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4478–4482. doi: 10.1073/pnas.85.12.4478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Ikuta K., Morita C., Miyake S., Ito T., Okabayashi M., Sano K., Nakai M., Hirai K., Kato S. Expression of human immunodeficiency virus type 1 (HIV-1) gag antigens on the surface of a cell line persistently infected with HIV-1 that highly expresses HIV-1 antigens. Virology. 1989 Jun;170(2):408–417. doi: 10.1016/0042-6822(89)90431-5. [DOI] [PubMed] [Google Scholar]
  19. Ishihara C., Miyazawa M., Nishio J., Chesebro B. Induction of protective immunity to Friend murine leukemia virus in genetic nonresponders to virus envelope protein. J Immunol. 1991 Jun 1;146(11):3958–3963. [PubMed] [Google Scholar]
  20. Kabat D. Molecular biology of Friend viral erythroleukemia. Curr Top Microbiol Immunol. 1989;148:1–42. doi: 10.1007/978-3-642-74700-7_1. [DOI] [PubMed] [Google Scholar]
  21. Klarnet J. P., Kern D. E., Okuno K., Holt C., Lilly F., Greenberg P. D. FBL-reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus-encoded antigens. J Exp Med. 1989 Feb 1;169(2):457–467. doi: 10.1084/jem.169.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lilly F. The effect of histocompatibility-2 type on response to friend leukemia virus in mice. J Exp Med. 1968 Mar 1;127(3):465–473. doi: 10.1084/jem.127.3.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mackett M., Smith G. L., Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol. 1984 Mar;49(3):857–864. doi: 10.1128/jvi.49.3.857-864.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
  25. Milich D. R., McLachlan A., Thornton G. B., Hughes J. L. Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site. Nature. 1987 Oct 8;329(6139):547–549. doi: 10.1038/329547a0. [DOI] [PubMed] [Google Scholar]
  26. Miyazawa M., Nishio J., Chesebro B. Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes. J Exp Med. 1988 Nov 1;168(5):1587–1605. doi: 10.1084/jem.168.5.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Miyazawa M., Nishio J., Wehrly K., Chesebro B. Influence of MHC genes on spontaneous recovery from Friend retrovirus-induced leukemia. J Immunol. 1992 Jan 15;148(2):644–647. [PubMed] [Google Scholar]
  28. Miyazawa M., Nose M., Kawashima M., Kyogoku M. Pathogenesis of arteritis of SL/Ni mice. Possible lytic effect of anti-gp70 antibodies on vascular smooth muscle cells. J Exp Med. 1987 Oct 1;166(4):890–908. doi: 10.1084/jem.166.4.890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Morrison R. P., Earl P. L., Nishio J., Lodmell D. L., Moss B., Chesebro B. Different H-2 subregions influence immunization against retrovirus and immunosuppression. Nature. 1987 Oct 22;329(6141):729–732. doi: 10.1038/329729a0. [DOI] [PubMed] [Google Scholar]
  30. Naylor P. H., Naylor C. W., Badamchian M., Wada S., Goldstein A. L., Wang S. S., Sun D. K., Thornton A. H., Sarin P. S. Human immunodeficiency virus contains an epitope immunoreactive with thymosin alpha 1 and the 30-amino acid synthetic p17 group-specific antigen peptide HGP-30. Proc Natl Acad Sci U S A. 1987 May;84(9):2951–2955. doi: 10.1073/pnas.84.9.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nixon D. F., Townsend A. R., Elvin J. G., Rizza C. R., Gallwey J., McMichael A. J. HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature. 1988 Dec 1;336(6198):484–487. doi: 10.1038/336484a0. [DOI] [PubMed] [Google Scholar]
  32. Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Perryman S., Nishio J., Chesebro B. Complete nucleotide sequence of Friend murine leukemia virus, strain FB29. Nucleic Acids Res. 1991 Dec 25;19(24):6950–6950. doi: 10.1093/nar/19.24.6950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Plata F., Langlade-Demoyen P., Abastado J. P., Berbar T., Kourilsky P. Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Cell. 1987 Jan 30;48(2):231–240. doi: 10.1016/0092-8674(87)90426-0. [DOI] [PubMed] [Google Scholar]
  35. Prats A. C., De Billy G., Wang P., Darlix J. L. CUG initiation codon used for the synthesis of a cell surface antigen coded by the murine leukemia virus. J Mol Biol. 1989 Jan 20;205(2):363–372. doi: 10.1016/0022-2836(89)90347-1. [DOI] [PubMed] [Google Scholar]
  36. Robertson M. N., Miyazawa M., Mori S., Caughey B., Evans L. H., Hayes S. F., Chesebro B. Production of monoclonal antibodies reactive with a denatured form of the Friend murine leukemia virus gp70 envelope protein: use in a focal infectivity assay, immunohistochemical studies, electron microscopy and western blotting. J Virol Methods. 1991 Oct;34(3):255–271. doi: 10.1016/0166-0934(91)90105-9. [DOI] [PubMed] [Google Scholar]
  37. Sarin P. S., Sun D. K., Thornton A. H., Naylor P. H., Goldstein A. L. Neutralization of HTLV-III/LAV replication by antiserum to thymosin alpha 1. Science. 1986 May 30;232(4754):1135–1137. doi: 10.1126/science.3010464. [DOI] [PubMed] [Google Scholar]
  38. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  39. Scherle P. A., Gerhard W. Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J Exp Med. 1986 Oct 1;164(4):1114–1128. doi: 10.1084/jem.164.4.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shang F., Huang H., Revesz K., Chen H. C., Herz R., Pinter A. Characterization of monoclonal antibodies against the human immunodeficiency virus matrix protein, p17gag: identification of epitopes exposed at the surfaces of infected cells. J Virol. 1991 Sep;65(9):4798–4804. doi: 10.1128/jvi.65.9.4798-4804.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sitbon M., Nishio J., Wehrly K., Lodmell D., Chesebro B. Use of a focal immunofluorescence assay on live cells for quantitation of retroviruses: distinction of host range classes in virus mixtures and biological cloning of dual-tropic murine leukemia viruses. Virology. 1985 Feb;141(1):110–118. doi: 10.1016/0042-6822(85)90187-4. [DOI] [PubMed] [Google Scholar]
  42. Sitbon M., Sola B., Evans L., Nishio J., Hayes S. F., Nathanson K., Garon C. F., Chesebro B. Hemolytic anemia and erythroleukemia, two distinct pathogenic effects of Friend MuLV: mapping of the effects to different regions of the viral genome. Cell. 1986 Dec 26;47(6):851–859. doi: 10.1016/0092-8674(86)90800-7. [DOI] [PubMed] [Google Scholar]
  43. Smith G. L., Murphy B. R., Moss B. Construction and characterization of an infectious vaccinia virus recombinant that expresses the influenza hemagglutinin gene and induces resistance to influenza virus infection in hamsters. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7155–7159. doi: 10.1073/pnas.80.23.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wahren B., Rosen J., Sandström E., Mathiesen T., Modrow S., Wigzell H. HIV-1 peptides induce a proliferative response in lymphocytes from infected persons. J Acquir Immune Defic Syndr. 1989;2(5):448–456. [PubMed] [Google Scholar]
  45. Walker B. D., Chakrabarti S., Moss B., Paradis T. J., Flynn T., Durno A. G., Blumberg R. S., Kaplan J. C., Hirsch M. S., Schooley R. T. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature. 1987 Jul 23;328(6128):345–348. doi: 10.1038/328345a0. [DOI] [PubMed] [Google Scholar]
  46. Wolfs T. F., de Jong J. J., Van den Berg H., Tijnagel J. M., Krone W. J., Goudsmit J. Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus 1 is host dependent, rapid, and continuous. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9938–9942. doi: 10.1073/pnas.87.24.9938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yuen L., Moss B. Oligonucleotide sequence signaling transcriptional termination of vaccinia virus early genes. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6417–6421. doi: 10.1073/pnas.84.18.6417. [DOI] [PMC free article] [PubMed] [Google Scholar]

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