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. 1997 Apr;71(4):3263–3267. doi: 10.1128/jvi.71.4.3263-3267.1997

Polyclonal bovine sera but not virus-neutralizing monoclonal antibodies block bovine leukemia virus (BLV) gp51 binding to recombinant BLV receptor BLVRcp1.

O Orlik 1, J Ban 1, J Hlavaty 1, C Altaner 1, R Kettmann 1, D Portetelle 1, G A Splitter 1
PMCID: PMC191461  PMID: 9060692

Abstract

Bovine leukemia virus (BLV), a transactivating lymphotropic retrovirus, is the etiologic agent of enzootic lymphosarcoma or leukemia in cattle. Sera from BLV-infected animals possess high BLV-neutralizing antibody titres. The availability of the recombinant BLV receptor candidate, BLVRcp1, allowed us to determine a mechanism of virus neutralization by polyclonal sera and monoclonal antibodies (MAbs). Bovine sera from animals naturally infected with BLV blocked gp51 binding to recombinant BLVRcp1. In contrast, virus-neutralizing MAbs specific for gp51 F, G, and H epitopes did not prevent gp51-receptor attachment. Furthermore, gp51 neutralization epitopes F, G, and H were accessible to antibodies following gp51 attachment to BLVRcp1. This finding implies that virus neutralization by MAbs to defined BLV gp51 epitopes can occur subsequent to virus engagement of the receptor while polyclonal sera can specifically block virus attachment to the receptor. In conclusion, these data suggest that cell infection by BLV is a multistep process requiring receptor binding (inhibited by polyclonal sera) followed by a second, postbinding event(s) at the cell membrane (inhibited by anti-gp51 MAbs).

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Selected References

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  1. Altaner C., Ban J., Altanerova V., Janik V. Protective vaccination against bovine leukaemia virus infection by means of cell-derived vaccine. Vaccine. 1991 Dec;9(12):889–895. doi: 10.1016/0264-410x(91)90009-u. [DOI] [PubMed] [Google Scholar]
  2. Altaner C., Bán J., Zajac V., Rössler H., Rosenthal S., Kettmann R., Burny A. Isolation and characterization of cell clones producing various amounts of bovine leukosis virus. Folia Biol (Praha) 1985;31(2):107–114. [PubMed] [Google Scholar]
  3. Altanerova V., Portetelle D., Kettmann R., Altaner C. Infection of rats with bovine leukaemia virus: establishment of a virus-producing rat cell line. J Gen Virol. 1989 Jul;70(Pt 7):1929–1932. doi: 10.1099/0022-1317-70-7-1929. [DOI] [PubMed] [Google Scholar]
  4. Astier T., Mamoun R., Guillemain B., Parodi A. L., Duplan J. F. Characterization of antibodies responsible for the inhibition of BLV induced early polycaryoxytosis. Ann Rech Vet. 1978;9(4):699–708. [PubMed] [Google Scholar]
  5. Ban J., Czene S., Altaner C., Callebaut I., Krchnak V., Merza M., Burny A., Kettmann R., Portetelle D. Mapping of sequential epitopes recognized by monoclonal antibodies on the bovine leukaemia virus external glycoproteins expressed in Escherichia coli by means of antipeptide antibodies. J Gen Virol. 1992 Sep;73(Pt 9):2457–2461. doi: 10.1099/0022-1317-73-9-2457. [DOI] [PubMed] [Google Scholar]
  6. Ban J., Gieciova E., Orlik O., Altaner C. Use of monoclonal antibodies in an ELISA for the diagnosis of bovine leukaemia virus infection. J Virol Methods. 1990 Oct;30(1):79–87. doi: 10.1016/0166-0934(90)90045-h. [DOI] [PubMed] [Google Scholar]
  7. Ban J., Portetelle D., Altaner C., Horion B., Milan D., Krchnak V., Burny A., Kettmann R. Isolation and characterization of a 2.3-kilobase-pair cDNA fragment encoding the binding domain of the bovine leukemia virus cell receptor. J Virol. 1993 Feb;67(2):1050–1057. doi: 10.1128/jvi.67.2.1050-1057.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ban J., Truong A. T., Horion B., Altaner C., Burny A., Portetelle D., Kettmann R. Isolation of the missing 5'-end of the encoding region of the bovine leukemia virus cell receptor gene. Arch Virol. 1994;138(3-4):379–383. doi: 10.1007/BF01379141. [DOI] [PubMed] [Google Scholar]
  9. Bex F., Bruck C., Mammerickx M., Portetelle D., Ghysdael J., Cleuter Y., Leclercq M., Dekegel D., Burny A. Humoral antibody response to bovine leukemia virus infection in cattle and sheep. Cancer Res. 1979 Mar;39(3):1118–1123. [PubMed] [Google Scholar]
  10. Broder C. C., Nussbaum O., Gutheil W. G., Bachovchin W. W., Berger E. A. CD26 antigen and HIV fusion? Science. 1994 May 20;264(5162):1156–1165. doi: 10.1126/science.7909959. [DOI] [PubMed] [Google Scholar]
  11. Bruck C., Mathot S., Portetelle D., Berte C., Franssen J. D., Herion P., Burny A. Monoclonal antibodies define eight independent antigenic regions on the bovine leukemia virus (BLV) envelope glycoprotein gp51. Virology. 1982 Oct 30;122(2):342–352. doi: 10.1016/0042-6822(82)90234-3. [DOI] [PubMed] [Google Scholar]
  12. Bruck C., Portetelle D., Mammerickx M., Mathot S., Burny A. Epitopes of bovine leukemia virus glycoprotein gp51 recognized by sera of infected cattle and sheep. Leuk Res. 1984;8(3):315–321. doi: 10.1016/0145-2126(84)90070-5. [DOI] [PubMed] [Google Scholar]
  13. Byrn R. A., Sekigawa I., Chamow S. M., Johnson J. S., Gregory T. J., Capon D. J., Groopman J. E. Characterization of in vitro inhibition of human immunodeficiency virus by purified recombinant CD4. J Virol. 1989 Oct;63(10):4370–4375. doi: 10.1128/jvi.63.10.4370-4375.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Callebaut C., Krust B., Jacotot E., Hovanessian A. G. T cell activation antigen, CD26, as a cofactor for entry of HIV in CD4+ cells. Science. 1993 Dec 24;262(5142):2045–2050. doi: 10.1126/science.7903479. [DOI] [PubMed] [Google Scholar]
  15. Callebaut I., Burny A., Krchnák V., Gras-Masse H., Wathelet B., Portetelle D. Use of synthetic peptides to map sequential epitopes recognized by monoclonal antibodies on the bovine leukemia virus external glycoprotein. Virology. 1991 Nov;185(1):48–55. doi: 10.1016/0042-6822(91)90752-w. [DOI] [PubMed] [Google Scholar]
  16. Callebaut I., Portetelle D., Burny A., Mornon J. P. Identification of functional sites on bovine leukemia virus envelope glycoproteins using structural and immunological data. Eur J Biochem. 1994 Jun 1;222(2):405–414. doi: 10.1111/j.1432-1033.1994.tb18879.x. [DOI] [PubMed] [Google Scholar]
  17. Chamat S., Nara P., Berquist L., Whalley A., Morrow W. J., Köhler H., Kang C. Y. Two major groups of neutralizing anti-gp120 antibodies exist in HIV-infected individuals. Evidence for epitope diversity around the CD4 attachment site. J Immunol. 1992 Jul 15;149(2):649–654. [PubMed] [Google Scholar]
  18. Chander S., Samagh B. S., Greig A. S. BLV-antibodies in serial sampling over five years in a bovine leukosis herd. Ann Rech Vet. 1978;9(4):797–802. [PubMed] [Google Scholar]
  19. Ivanoff L. A., Dubay J. W., Morris J. F., Roberts S. J., Gutshall L., Sternberg E. J., Hunter E., Matthews T. J., Petteway S. R., Jr V3 loop region of the HIV-1 gp120 envelope protein is essential for virus infectivity. Virology. 1992 Apr;187(2):423–432. doi: 10.1016/0042-6822(92)90444-t. [DOI] [PubMed] [Google Scholar]
  20. Kono Y., Arai K., Sentsui H., Matsukawa S., Itohara S. Protection against bovine leukemia virus infection in sheep by active and passive immunization. Nihon Juigaku Zasshi. 1986 Feb;48(1):117–125. doi: 10.1292/jvms1939.48.117. [DOI] [PubMed] [Google Scholar]
  21. Marlin S. D., Staunton D. E., Springer T. A., Stratowa C., Sommergruber W., Merluzzi V. J. A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection. Nature. 1990 Mar 1;344(6261):70–72. doi: 10.1038/344070a0. [DOI] [PubMed] [Google Scholar]
  22. Meiron R., Brenner J., Gluckman A., Avraham R., Trainin Z. Humoral and cellular responses in calves experimentally infected with bovine leukemia virus (BLV). Vet Immunol Immunopathol. 1985 Jun;9(2):105–114. doi: 10.1016/0165-2427(85)90011-x. [DOI] [PubMed] [Google Scholar]
  23. Merza M., Söber J., Sundquist B., Toots I., Morein B. Characterization of purified gp 51 from bovine leukemia virus integrated into iscom. Physicochemical properties and serum antibody response to the integrated gp51. Arch Virol. 1991;120(3-4):219–231. doi: 10.1007/BF01310477. [DOI] [PubMed] [Google Scholar]
  24. Moore M. D., Cannon M. J., Sewall A., Finlayson M., Okimoto M., Nemerow G. R. Inhibition of Epstein-Barr virus infection in vitro and in vivo by soluble CR2 (CD21) containing two short consensus repeats. J Virol. 1991 Jul;65(7):3559–3565. doi: 10.1128/jvi.65.7.3559-3565.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Onuma M., Hodatsu T., Yamamoto S., Higashihara M., Masu S., Mikami T., Izawa H. Protection by vaccination against bovine leukemia virus infection in sheep. Am J Vet Res. 1984 Jun;45(6):1212–1215. [PubMed] [Google Scholar]
  26. Orlik O., Ban J., Gieciova E., Altanerova V., Altaner C. Two immunodominant regions revealed by monoclonal antibodies on the main structural protein p24 of bovine leukemia virus. Viral Immunol. 1993 Winter;6(4):245–254. doi: 10.1089/vim.1993.6.245. [DOI] [PubMed] [Google Scholar]
  27. Orlík O., Bán J., Gieciová E., Altanerová V., Altaner C. Preparation and characterization of monoclonal antibodies directed against glycoproteins of bovine leukaemia virus. Acta Virol. 1993 Oct;37(5):377–387. [PubMed] [Google Scholar]
  28. Popescu C. P., Boscher J., Hayes H. C., Ban J., Kettmann R. Chromosomal localization of the BLV receptor candidate gene in cattle, sheep, and goat. Cytogenet Cell Genet. 1995;69(1-2):50–52. doi: 10.1159/000133936. [DOI] [PubMed] [Google Scholar]
  29. Portetelle D., Bruck C., Burny A., Dekegel D., Mammerickx M., Urbain J. Detection of complement-dependent lytic antibodies in sera from bovine leukemia virus-infected animals. Ann Rech Vet. 1978;9(4):667–674. [PubMed] [Google Scholar]
  30. Portetelle D., Couez D., Bruck C., Kettmann R., Mammerickx M., Van der Maaten M., Brasseur R., Burny A. Antigenic variants of bovine leukemia virus (BLV) are defined by amino acid substitutions in the NH2 part of the envelope glycoprotein gp51. Virology. 1989 Mar;169(1):27–33. doi: 10.1016/0042-6822(89)90037-8. [DOI] [PubMed] [Google Scholar]
  31. Portetelle D., Dandoy C., Burny A., Zavada J., Siakkou H., Gras-Masse H., Drobecq H., Tartar A. Synthetic peptides approach to identification of epitopes on bovine leukemia virus envelope glycoprotein gp51. Virology. 1989 Mar;169(1):34–41. doi: 10.1016/0042-6822(89)90038-x. [DOI] [PubMed] [Google Scholar]
  32. Portetelle D., Mammerickx M., Burny A. Use of two monoclonal antibodies in an ELISA test for the detection of antibodies to bovine leukaemia virus envelope protein gp51. J Virol Methods. 1989 Feb;23(2):211–222. doi: 10.1016/0166-0934(89)90135-3. [DOI] [PubMed] [Google Scholar]
  33. Powers M. A., Grossman D., Kidd L. C., Radke K. Episodic occurrence of antibodies against the bovine leukemia virus Rex protein during the course of infection in sheep. J Virol. 1991 Sep;65(9):4959–4965. doi: 10.1128/jvi.65.9.4959-4965.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schwartz I., Lévy D. Pathobiology of bovine leukemia virus. Vet Res. 1994;25(6):521–536. [PubMed] [Google Scholar]
  35. Skinner M. A., Langlois A. J., McDanal C. B., McDougal J. S., Bolognesi D. P., Matthews T. J. Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J Virol. 1988 Nov;62(11):4195–4200. doi: 10.1128/jvi.62.11.4195-4200.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stocco R., Sauvageau G., Stefanescu I., Menezes J. Effect of monoclonal antibodies to Epstein-Barr virus envelope glycoproteins on Epstein-Barr virus neutralization and binding to target cell receptors. A comparative analysis. Intervirology. 1990;31(5):295–300. doi: 10.1159/000150165. [DOI] [PubMed] [Google Scholar]
  37. Vonèche V., Portetelle D., Kettmann R., Willems L., Limbach K., Paoletti E., Ruysschaert J. M., Burny A., Brasseur R. Fusogenic segments of bovine leukemia virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target cells. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3810–3814. doi: 10.1073/pnas.89.9.3810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Willey R. L., Martin M. A., Peden K. W. Increase in soluble CD4 binding to and CD4-induced dissociation of gp120 from virions correlates with infectivity of human immunodeficiency virus type 1. J Virol. 1994 Feb;68(2):1029–1039. doi: 10.1128/jvi.68.2.1029-1039.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Závada J., Cerný L., Altstein A. D., Závadová Z. Pseudotype particles of vesicular stomatitis virus with surface antigens of bovine leukaemia virus--VSV (BLV) -- as a sensitive probe for detecting antibodies in the sera of spontaneously infected cattle. Acta Virol. 1978 Mar;22(2):91–96. [PubMed] [Google Scholar]

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