Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1993 Feb;67(2):961–968. doi: 10.1128/jvi.67.2.961-968.1993

An antibody- and synthetic peptide-defined rubella virus E1 glycoprotein neutralization domain.

J S Wolinsky 1, E Sukholutsky 1, W T Moore 1, A Lovett 1, M McCarthy 1, B Adame 1
PMCID: PMC237450  PMID: 7678312

Abstract

We previously described a monoclonal antibody (MAb) library generated by infecting BALB/c mice with rubella virus (RV) and selected by an enzyme-linked immunosorbent assay (ELISA) using purified virion targets. Plasmid pARV02-01, which expresses the fusion protein RecA1-35-GIGDLGSP-E1(202)-E1(283)-GDP-LacZ9-1015 in Escherichia coli, was shown to be a ligand for MAbs E1-18 and E1-20 (J. S. Wolinsky, M. McCarthy, O. Allen-Cannady, W. T. Moore, R. Jin, S. N. Cao, A. Lovett, and D. Simmons, J. Virol. 65:3986-3994, 1991). Both of these MAbs neutralize RV infectivity. A series of five overlapping synthetic peptides was made to further explore the requirements of this MAb binding domain. One of these peptides (SP15; E1(208) to E1(239)) proved an effective ligand for both MAbs in the ELISA. Stepwise synthesis of SP15 defined the minimal amino-terminal requirement for binding MAb E1-18 as E1(221) and that of MAb E1-20 as E1(223); the minimal carboxyl-terminal requirement is uncertain but does not exceed E1(239). Immunization of mice and rabbits with SP15 induced polyvalent antibody reactive with SP15, with other overlapped and related but not unrelated synthetic peptides, and with RV. The rabbit anti-SP15 antibody showed neutralization activity to RV similar to that of MAbs E1-18 and E1-20 but lacked hemagglutination inhibition activity. These data define a neutralization domain on E1 and suggest that the RV epitopes conserved by SP15 may be critical for protective host humoral immune responses.

Full text

PDF
961

Selected References

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

  1. Atassi M. Z., Webster R. G. Localization, synthesis, and activity of an antigenic site on influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1983 Feb;80(3):840–844. doi: 10.1073/pnas.80.3.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baron M. D., Forsell K. Oligomerization of the structural proteins of rubella virus. Virology. 1991 Dec;185(2):811–819. doi: 10.1016/0042-6822(91)90552-m. [DOI] [PubMed] [Google Scholar]
  3. Caprioli R. M., Moore W. T. Continuous-flow fast atom bombardment mass spectrometry. Methods Enzymol. 1990;193:214–237. doi: 10.1016/0076-6879(90)93417-j. [DOI] [PubMed] [Google Scholar]
  4. Chaye H., Chong P., Tripet B., Brush B., Gillam S. Localization of the virus neutralizing and hemagglutinin epitopes of E1 glycoprotein of rubella virus. Virology. 1992 Aug;189(2):483–492. doi: 10.1016/0042-6822(92)90572-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clarke D. M., Loo T. W., Hui I., Chong P., Gillam S. Nucleotide sequence and in vitro expression of rubella virus 24S subgenomic messenger RNA encoding the structural proteins E1, E2 and C. Nucleic Acids Res. 1987 Apr 10;15(7):3041–3057. doi: 10.1093/nar/15.7.3041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DiMarchi R., Brooke G., Gale C., Cracknell V., Doel T., Mowat N. Protection of cattle against foot-and-mouth disease by a synthetic peptide. Science. 1986 May 2;232(4750):639–641. doi: 10.1126/science.3008333. [DOI] [PubMed] [Google Scholar]
  7. Dietzschold B., Gore M., Marchadier D., Niu H. S., Bunschoten H. M., Otvos L., Jr, Wunner W. H., Ertl H. C., Osterhaus A. D., Koprowski H. Structural and immunological characterization of a linear virus-neutralizing epitope of the rabies virus glycoprotein and its possible use in a synthetic vaccine. J Virol. 1990 Aug;64(8):3804–3809. doi: 10.1128/jvi.64.8.3804-3809.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doel T. R., Doel C. M., Staple R. F., DiMarchi R. Cross-reactive and serotype-specific antibodies against foot-and-mouth disease virus generated by different regions of the same synthetic peptide. J Virol. 1992 Apr;66(4):2187–2194. doi: 10.1128/jvi.66.4.2187-2194.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dominguez G., Wang C. Y., Frey T. K. Sequence of the genome RNA of rubella virus: evidence for genetic rearrangement during togavirus evolution. Virology. 1990 Jul;177(1):225–238. doi: 10.1016/0042-6822(90)90476-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Frey T. K., Marr L. D., Hemphill M. L., Dominguez G. Molecular cloning and sequencing of the region of the rubella virus genome coding for glycoprotein E1. Virology. 1986 Oct 15;154(1):228–232. doi: 10.1016/0042-6822(86)90446-0. [DOI] [PubMed] [Google Scholar]
  11. Gerna I., Zannino M., Revello M. G., Petruzzelli E., Dovis M. Development and evaluation of a capture enzyme-linked immunosorbent assay for determination of rubella immunoglobulin M using monoclonal antibodies. J Clin Microbiol. 1987 Jun;25(6):1033–1038. doi: 10.1128/jcm.25.6.1033-1038.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Green K. Y., Dorsett P. H. Rubella virus antigens: localization of epitopes involved in hemagglutination and neutralization by using monoclonal antibodies. J Virol. 1986 Mar;57(3):893–898. doi: 10.1128/jvi.57.3.893-898.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Green N., Alexander H., Olson A., Alexander S., Shinnick T. M., Sutcliffe J. G., Lerner R. A. Immunogenic structure of the influenza virus hemagglutinin. Cell. 1982 Mar;28(3):477–487. doi: 10.1016/0092-8674(82)90202-1. [DOI] [PubMed] [Google Scholar]
  14. Greenstein J. L., Schad V. C., Goodwin W. H., Brauer A. B., Bollinger B. K., Chin R. D., Kuo M. C. A universal T cell epitope-containing peptide from hepatitis B surface antigen can enhance antibody specific for HIV gp120. J Immunol. 1992 Jun 15;148(12):3970–3977. [PubMed] [Google Scholar]
  15. Hart M. K., Palker T. J., Matthews T. J., Langlois A. J., Lerche N. W., Martin M. E., Scearce R. M., McDanal C., Bolognesi D. P., Haynes B. F. Synthetic peptides containing T and B cell epitopes from human immunodeficiency virus envelope gp120 induce anti-HIV proliferative responses and high titers of neutralizing antibodies in rhesus monkeys. J Immunol. 1990 Oct 15;145(8):2677–2685. [PubMed] [Google Scholar]
  16. Ho-Terry L., Cohen A. Rubella virus haemagglutinin: association with a single virion glycoprotein. Arch Virol. 1985;84(3-4):207–215. doi: 10.1007/BF01378973. [DOI] [PubMed] [Google Scholar]
  17. Ho-Terry L., Terry G. M., Cohen A., Londesborough P. Immunological characterisation of the rubella E 1 glycoprotein. Brief report. Arch Virol. 1986;90(1-2):145–152. doi: 10.1007/BF01314152. [DOI] [PubMed] [Google Scholar]
  18. Hunt A. R., Johnson A. J., Roehrig J. T. Synthetic peptides of Venezuelan equine encephalomyelitis virus E2 glycoprotein. I. Immunogenic analysis and identification of a protective peptide. Virology. 1990 Dec;179(2):701–711. doi: 10.1016/0042-6822(90)90137-g. [DOI] [PubMed] [Google Scholar]
  19. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  20. Laman J. D., Schellekens M. M., Abacioglu Y. H., Lewis G. K., Tersmette M., Fouchier R. A., Langedijk J. P., Claassen E., Boersma W. J. Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain. J Virol. 1992 Mar;66(3):1823–1831. doi: 10.1128/jvi.66.3.1823-1831.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Laver W. G., Air G. M., Webster R. G., Smith-Gill S. J. Epitopes on protein antigens: misconceptions and realities. Cell. 1990 May 18;61(4):553–556. doi: 10.1016/0092-8674(90)90464-p. [DOI] [PubMed] [Google Scholar]
  22. Lozzi L., Rustici M., Corti M., Cusi M. G., Valensin P. E., Bracci L., Santucci A., Soldani P., Spreafico A., Neri P. Structure of rubella E1 glycoprotein epitopes established by multiple peptide synthesis. Arch Virol. 1990;110(3-4):271–276. doi: 10.1007/BF01311295. [DOI] [PubMed] [Google Scholar]
  23. Manivel V., Ramesh R., Panda S. K., Rao K. V. A synthetic peptide spontaneously self-assembles to reconstruct a group-specific, conformational determinant of hepatitis B surface antigen. J Immunol. 1992 Jun 15;148(12):4006–4011. [PubMed] [Google Scholar]
  24. McCarthy M., Lovett A., Kerman R. H., Overstreet A., Wolinsky J. S. Immunodominant T-cell epitopes of rubella virus structural proteins defined by synthetic peptides. J Virol. 1993 Feb;67(2):673–681. doi: 10.1128/jvi.67.2.673-681.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McCray J., Werner G. Different rhinovirus serotypes neutralized by antipeptide antibodies. Nature. 1987 Oct 22;329(6141):736–738. doi: 10.1038/329736a0. [DOI] [PubMed] [Google Scholar]
  26. Mitchell L. A., Zhang T., Ho M., Décarie D., Tingle A. J., Zrein M., Lacroix M. Characterization of rubella virus-specific antibody responses by using a new synthetic peptide-based enzyme-linked immunosorbent assay. J Clin Microbiol. 1992 Jul;30(7):1841–1847. doi: 10.1128/jcm.30.7.1841-1847.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nakhasi H. L., Zheng D., Callahan L., Dave J. R., Liu T. Y. Rubella virus: mechanism of attenuation in the vaccine strain (HPV77). Virus Res. 1989 Jul;13(3):231–243. doi: 10.1016/0168-1702(89)90018-x. [DOI] [PubMed] [Google Scholar]
  28. Neri P., Corti M., Lozzi L., Valensin P. E. Structure and antigenic activity of rubella E1 glycoprotein synthetic peptides. Biopolymers. 1991 May;31(6):631–635. doi: 10.1002/bip.360310607. [DOI] [PubMed] [Google Scholar]
  29. Neurath A. R., Kent S. B., Parker K., Prince A. M., Strick N., Brotman B., Sproul P. Antibodies to a synthetic peptide from the preS 120-145 region of the hepatitis B virus envelope are virus neutralizing. Vaccine. 1986 Mar;4(1):35–37. doi: 10.1016/s0264-410x(86)80001-9. [DOI] [PubMed] [Google Scholar]
  30. Partidos C., Stanley C., Steward M. The effect of orientation of epitopes on the immunogenicity of chimeric synthetic peptides representing measles virus protein sequences. Mol Immunol. 1992 May;29(5):651–658. doi: 10.1016/0161-5890(92)90202-9. [DOI] [PubMed] [Google Scholar]
  31. Roehrig J. T., Hunt A. R., Johnson A. J., Hawkes R. A. Synthetic peptides derived from the deduced amino acid sequence of the E-glycoprotein of Murray Valley encephalitis virus elicit antiviral antibody. Virology. 1989 Jul;171(1):49–60. doi: 10.1016/0042-6822(89)90509-6. [DOI] [PubMed] [Google Scholar]
  32. Roehrig J. T., Johnson A. J., Hunt A. R., Beaty B. J., Mathews J. H. Enhancement of the antibody response to flavivirus B-cell epitopes by using homologous or heterologous T-cell epitopes. J Virol. 1992 Jun;66(6):3385–3390. doi: 10.1128/jvi.66.6.3385-3390.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sakaguchi K., Appella E., Omichinski J. G., Clore G. M., Gronenborn A. M. Specific DNA binding to a major histocompatibility complex enhancer sequence by a synthetic 57-residue double zinc finger peptide from a human enhancer binding protein. J Biol Chem. 1991 Apr 15;266(11):7306–7311. [PubMed] [Google Scholar]
  34. Shapira M., Jibson M., Muller G., Arnon R. Immunity and protection against influenza virus by synthetic peptide corresponding to antigenic sites of hemagglutinin. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2461–2465. doi: 10.1073/pnas.81.8.2461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Snijders A., Benaissa-Trouw B. J., Oosterlaken T. A., Puijk W. C., Posthumus W. P., Meloen R. H., Boere W. A., Oosting J. D., Kraaijeveld C. A., Snippe H. Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine. J Gen Virol. 1991 Mar;72(Pt 3):557–565. doi: 10.1099/0022-1317-72-3-557. [DOI] [PubMed] [Google Scholar]
  36. Terry G. M., Ho-Terry L., Londesborough P., Rees K. R. Localization of the rubella E1 epitopes. Arch Virol. 1988;98(3-4):189–197. doi: 10.1007/BF01322168. [DOI] [PubMed] [Google Scholar]
  37. Tripathy S. P., Kumar A., Manivel V., Panda S. K., Rao K. V. Design and synthesis of a self-assembling peptide derived from the envelope proteins of HIV type 1. An approach to heterovalent immunogens. J Immunol. 1992 Jun 15;148(12):4012–4020. [PubMed] [Google Scholar]
  38. Trudel M., Nadon F., Séguin C., Amarouch A., Payment P., Gillam S. E1 glycoprotein of rubella virus carries an epitope that binds a neutralizing antibody. J Virol Methods. 1985 Dec;12(3-4):243–250. doi: 10.1016/0166-0934(85)90135-1. [DOI] [PubMed] [Google Scholar]
  39. Vidgren G., Takkinen K., Kalkkinen N., Käriäinen L., Pettersson R. F. Nucleotide sequence of the genes coding for the membrane glycoproteins E1 and E2 of rubella virus. J Gen Virol. 1987 Sep;68(Pt 9):2347–2357. doi: 10.1099/0022-1317-68-9-2347. [DOI] [PubMed] [Google Scholar]
  40. Waxham M. N., Wolinsky J. S. A model of the structural organization of rubella virions. Rev Infect Dis. 1985 Mar-Apr;7 (Suppl 1):S133–S139. doi: 10.1093/clinids/7.supplement_1.s133. [DOI] [PubMed] [Google Scholar]
  41. Waxham M. N., Wolinsky J. S. Detailed immunologic analysis of the structural polypeptides of rubella virus using monoclonal antibodies. Virology. 1985 May;143(1):153–165. doi: 10.1016/0042-6822(85)90104-7. [DOI] [PubMed] [Google Scholar]
  42. Waxham M. N., Wolinsky J. S. Immunochemical identification of rubella virus hemagglutinin. Virology. 1983 Apr 15;126(1):194–203. doi: 10.1016/0042-6822(83)90471-3. [DOI] [PubMed] [Google Scholar]
  43. Wittenburg R. A., Roberts M. A., Elliott L. B., Little L. M. Comparative evaluation of commercial rubella virus antibody kits. J Clin Microbiol. 1985 Feb;21(2):161–163. doi: 10.1128/jcm.21.2.161-163.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wlodawer A., Miller M., Jaskólski M., Sathyanarayana B. K., Baldwin E., Weber I. T., Selk L. M., Clawson L., Schneider J., Kent S. B. Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science. 1989 Aug 11;245(4918):616–621. doi: 10.1126/science.2548279. [DOI] [PubMed] [Google Scholar]
  45. Wolinsky J. S., McCarthy M., Allen-Cannady O., Moore W. T., Jin R., Cao S. N., Lovett A., Simmons D. Monoclonal antibody-defined epitope map of expressed rubella virus protein domains. J Virol. 1991 Aug;65(8):3986–3994. doi: 10.1128/jvi.65.8.3986-3994.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Zheng D. X., Dickens L., Liu T. Y., Nakhasi H. L. Nucleotide sequence of the 24S subgenomic messenger RNA of a vaccine strain (HPV77) of rubella virus: comparison with a wild-type strain (M33). Gene. 1989 Oct 30;82(2):343–349. doi: 10.1016/0378-1119(89)90061-9. [DOI] [PubMed] [Google Scholar]
  47. Zwart G., Langedijk H., van der Hoek L., de Jong J. J., Wolfs T. F., Ramautarsing C., Bakker M., de Ronde A., Goudsmit J. Immunodominance and antigenic variation of the principal neutralization domain of HIV-1. Virology. 1991 Apr;181(2):481–489. doi: 10.1016/0042-6822(91)90880-k. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES