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. 1991 Dec;65(12):6862–6871. doi: 10.1128/jvi.65.12.6862-6871.1991

Antigenic and immunogenic epitopes shared by human papillomavirus type 16 and bovine, canine, and avian papillomaviruses.

L Dillner 1, P Heino 1, J Moreno-Lopez 1, J Dillner 1
PMCID: PMC250784  PMID: 1719234

Abstract

All types of papillomaviruses (PV) share common, so-called group-specific epitopes. To identify the major group-specific epitopes, we immunized 26 guinea pigs or rabbits with purified bovine PV type 1 (BPV), canine PV, or avian PV from the common chaffinch. The resulting hyperimmune sera, as well as a commercially available rabbit antiserum to BPV and seven monoclonal antibodies to BPV, were tested in an enzyme-linked immunosorbent assay with a set of 66 overlapping 20-amino-acid peptides representing the complete sequence of the major capsid proteins (L1 and L2) of human PV type 16 (HPV 16). Sera from the same animals before immunization were used as controls. The minimal reactive epitopes within each peptide were further characterized by testing of truncated peptides. The cross-reactive epitopes were clustered in two regions of L1, an internal region (at positions 171 to 235), which contained three epitopes, and the more reactive region at the carboxy terminus (at positions 411 to 475), which contained six epitopes. The most reactive of the HPV 16 broadly cross-reactive epitopes was a carboxy-terminal epitope which had the sequence DTYRF and which reacted with nine of the antisera to BPV, canine PV, or avian PV, with the commercially available rabbit antiserum to BPV, and also with a mouse monoclonal antibody to BPV. Antipeptide antisera to all of the HPV 16 L1 peptides and to the most antigenically reactive of their truncated analogs were made in guinea pigs. Antipeptide antisera reactive with BPV were obtained for three of the cross-reactive epitopes, and one of these antisera allowed highly sensitive detection of group-specific PV antigen by immunoperoxidase staining.

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Selected References

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  1. Banks L., Matlashewski G., Pim D., Churcher M., Roberts C., Crawford L. Expression of human papillomavirus type 6 and type 16 capsid proteins in bacteria and their antigenic characterization. J Gen Virol. 1987 Dec;68(Pt 12):3081–3089. doi: 10.1099/0022-1317-68-12-3081. [DOI] [PubMed] [Google Scholar]
  2. Blomberg J., Nilsson I., Andersson M. Viral antibody screening system that uses a standardized single dilution immunoglobulin G enzyme immunoassay with multiple antigens. J Clin Microbiol. 1983 Jun;17(6):1081–1091. doi: 10.1128/jcm.17.6.1081-1091.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cason J., Patel D., Naylor J., Lunney D., Shepherd P. S., Best J. M., McCance D. J. Identification of immunogenic regions of the major coat protein of human papillomavirus type 16 that contain type-restricted epitopes. J Gen Virol. 1989 Nov;70(Pt 11):2973–2987. doi: 10.1099/0022-1317-70-11-2973. [DOI] [PubMed] [Google Scholar]
  4. Christensen N. D., Kreider J. W., Cladel N. M., Galloway D. A. Immunological cross-reactivity to laboratory-produced HPV-11 virions of polysera raised against bacterially derived fusion proteins and synthetic peptides of HPV-6b and HPV-16 capsid proteins. Virology. 1990 Mar;175(1):1–9. doi: 10.1016/0042-6822(90)90180-y. [DOI] [PubMed] [Google Scholar]
  5. Cowsert L. M., Lake P., Jenson A. B. Topographical and conformational epitopes of bovine papillomavirus type 1 defined by monoclonal antibodies. J Natl Cancer Inst. 1987 Nov;79(5):1053–1057. [PubMed] [Google Scholar]
  6. Dillner J., Dillner L., Robb J., Willems J., Jones I., Lancaster W., Smith R., Lerner R. A synthetic peptide defines a serologic IgA response to a human papillomavirus-encoded nuclear antigen expressed in virus-carrying cervical neoplasia. Proc Natl Acad Sci U S A. 1989 May;86(10):3838–3841. doi: 10.1073/pnas.86.10.3838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dillner J., Dillner L., Utter G., Eklund C., Rotola A., Costa S., DiLuca D. Mapping of linear epitopes of human papillomavirus type 16: the L1 and L2 open reading frames. Int J Cancer. 1990 Mar 15;45(3):529–535. doi: 10.1002/ijc.2910450326. [DOI] [PubMed] [Google Scholar]
  8. Dillner J. Mapping of linear epitopes of human papillomavirus type 16: the E1, E2, E4, E5, E6 and E7 open reading frames. Int J Cancer. 1990 Oct 15;46(4):703–711. doi: 10.1002/ijc.2910460426. [DOI] [PubMed] [Google Scholar]
  9. Dillner L., Bekassy Z., Jonsson N., Moreno-Lopez J., Blomberg J. Detection of IgA antibodies against human papillomavirus in cervical secretions from patients with cervical intraepithelial neoplasia. Int J Cancer. 1989 Jan 15;43(1):36–40. doi: 10.1002/ijc.2910430109. [DOI] [PubMed] [Google Scholar]
  10. Dillner L., Moreno-Lopez J., Dillner J. Serological responses to papillomavirus group-specific antigens in women with neoplasia of the cervix uteri. J Clin Microbiol. 1990 Mar;28(3):624–627. doi: 10.1128/jcm.28.3.624-627.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dyson H. J., Cross K. J., Houghten R. A., Wilson I. A., Wright P. E., Lerner R. A. The immunodominant site of a synthetic immunogen has a conformational preference in water for a type-II reverse turn. Nature. 1985 Dec 5;318(6045):480–483. doi: 10.1038/318480a0. [DOI] [PubMed] [Google Scholar]
  12. Fieser T. M., Tainer J. A., Geysen H. M., Houghten R. A., Lerner R. A. Influence of protein flexibility and peptide conformation on reactivity of monoclonal anti-peptide antibodies with a protein alpha-helix. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8568–8572. doi: 10.1073/pnas.84.23.8568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fridell E., Trojnar J., Wahren B. A new peptide for human parvovirus B19 antibody detection. Scand J Infect Dis. 1989;21(6):597–603. doi: 10.3109/00365548909021686. [DOI] [PubMed] [Google Scholar]
  14. Geysen H. M., Mason T. J., Rodda S. J. Cognitive features of continuous antigenic determinants. J Mol Recognit. 1988 Feb;1(1):32–41. doi: 10.1002/jmr.300010107. [DOI] [PubMed] [Google Scholar]
  15. Granström M., Julander I. G., Hedström S. A., Möllby R. Enzyme-linked immunosorbent assay for antibodies against teichoic acid in patients with staphylococcal infections. J Clin Microbiol. 1983 Apr;17(4):640–646. doi: 10.1128/jcm.17.4.640-646.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jenison S. A., Yu X. P., Valentine J. M., Galloway D. A. Human antibodies react with an epitope of the human papillomavirus type 6b L1 open reading frame which is distinct from the type-common epitope. J Virol. 1989 Feb;63(2):809–818. doi: 10.1128/jvi.63.2.809-818.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jenson A. B., Rosenthal J. D., Olson C., Pass F., Lancaster W. D., Shah K. Immunologic relatedness of papillomaviruses from different species. J Natl Cancer Inst. 1980 Mar;64(3):495–500. [PubMed] [Google Scholar]
  19. Komly C. A., Breitburd F., Croissant O., Streeck R. E. The L2 open reading frame of human papillomavirus type 1a encodes a minor structural protein carrying type-specific antigens. J Virol. 1986 Nov;60(2):813–816. doi: 10.1128/jvi.60.2.813-816.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kurman R. J., Jenson A. B., Lancaster W. D. Papillomavirus infection of the cervix. II. Relationship to intraepithelial neoplasia based on the presence of specific viral structural proteins. Am J Surg Pathol. 1983 Jan;7(1):39–52. [PubMed] [Google Scholar]
  21. Kurstak E. Progress in enzyme immunoassays: production of reagents, experimental design, and interpretation. Bull World Health Organ. 1985;63(4):793–811. [PMC free article] [PubMed] [Google Scholar]
  22. Li C. C., Shah K. V., Seth A., Gilden R. V. Identification of the human papillomavirus type 6b L1 open reading frame protein in condylomas and corresponding antibodies in human sera. J Virol. 1987 Sep;61(9):2684–2690. doi: 10.1128/jvi.61.9.2684-2690.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lim P. S., Jenson A. B., Cowsert L., Nakai Y., Lim L. Y., Jin X. W., Sundberg J. P. Distribution and specific identification of papillomavirus major capsid protein epitopes by immunocytochemistry and epitope scanning of synthetic peptides. J Infect Dis. 1990 Dec;162(6):1263–1269. doi: 10.1093/infdis/162.6.1263. [DOI] [PubMed] [Google Scholar]
  24. Linde A., Kallin B., Dillner J., Andersson J., Jägdahl L., Lindvall A., Wahren B. Evaluation of enzyme-linked immunosorbent assays with two synthetic peptides of Epstein-Barr virus for diagnosis of infectious mononucleosis. J Infect Dis. 1990 May;161(5):903–909. doi: 10.1093/infdis/161.5.903. [DOI] [PubMed] [Google Scholar]
  25. Morin C., Braun L., Casas-Cordero M., Shah K. V., Roy M., Fortier M., Meisels A. Confirmation of the papillomavirus etiology of condylomatous cervix lesions by the peroxidase-antiperoxidase technique. J Natl Cancer Inst. 1981 May;66(5):831–835. [PubMed] [Google Scholar]
  26. Müller M., Gausepohl H., de Martynoff G., Frank R., Brasseur R., Gissmann L. Identification of seroreactive regions of the human papillomavirus type 16 protein E4, E6, E7 and L1. J Gen Virol. 1990 Nov;71(Pt 11):2709–2717. doi: 10.1099/0022-1317-71-11-2709. [DOI] [PubMed] [Google Scholar]
  27. Nakai Y., Lancaster W. D., Lim L. Y., Jenson A. B. Monoclonal antibodies to genus- and type-specific papillomavirus structural antigens. Intervirology. 1986;25(1):30–37. doi: 10.1159/000149652. [DOI] [PubMed] [Google Scholar]
  28. Norrby E., Biberfeld G., Chiodi F., von Gegerfeldt A., Nauclér A., Parks E., Lerner R. Discrimination between antibodies to HIV and to related retroviruses using site-directed serology. Nature. 1987 Sep 17;329(6136):248–250. doi: 10.1038/329248a0. [DOI] [PubMed] [Google Scholar]
  29. Orth G., Breitburd F., Favre M. Evidence for antigenic determinants shared by the structural polypeptides of (Shope) rabbit papillomavirus and human papillomavirus type 1. Virology. 1978 Dec;91(2):243–255. doi: 10.1016/0042-6822(78)90373-2. [DOI] [PubMed] [Google Scholar]
  30. Parton A. Nucleotide sequence of the HPV16 L1 open reading frame. Nucleic Acids Res. 1990 Jun 25;18(12):3631–3631. doi: 10.1093/nar/18.12.3631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Patel D., Shepherd P. S., Naylor J. A., McCance D. J. Reactivities of polyclonal and monoclonal antibodies raised to the major capsid protein of human papillomavirus type 16. J Gen Virol. 1989 Jan;70(Pt 1):69–77. doi: 10.1099/0022-1317-70-1-69. [DOI] [PubMed] [Google Scholar]
  32. Seedorf K., Krämmer G., Dürst M., Suhai S., Röwekamp W. G. Human papillomavirus type 16 DNA sequence. Virology. 1985 Aug;145(1):181–185. doi: 10.1016/0042-6822(85)90214-4. [DOI] [PubMed] [Google Scholar]
  33. Steele J. C., Gallimore P. H. Humoral assays of human sera to disrupted and nondisrupted epitopes of human papillomavirus type 1. Virology. 1990 Feb;174(2):388–398. doi: 10.1016/0042-6822(90)90092-6. [DOI] [PubMed] [Google Scholar]
  34. Strike D. G., Bonnez W., Rose R. C., Reichman R. C. Expression in Escherichia coli of seven DNA fragments comprising the complete L1 and L2 open reading frames of human papillomavirus type 6b and localization of the 'common antigen' region. J Gen Virol. 1989 Mar;70(Pt 3):543–555. doi: 10.1099/0022-1317-70-3-543. [DOI] [PubMed] [Google Scholar]
  35. Tomita Y., Shirasawa H., Sekine H., Simizu B. Expression of the human papillomavirus type 6b L2 open reading frame in Escherichia coli: L2-beta-galactosidase fusion proteins and their antigenic properties. Virology. 1987 May;158(1):8–14. doi: 10.1016/0042-6822(87)90231-5. [DOI] [PubMed] [Google Scholar]
  36. Tomita Y., Shirasawa H., Simizu B. Expression of human papillomavirus types 6b and 16 L1 open reading frames in Escherichia coli: detection of a 56,000-dalton polypeptide containing genus-specific (common) antigens. J Virol. 1987 Aug;61(8):2389–2394. doi: 10.1128/jvi.61.8.2389-2394.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Woodruff J. D., Braun L., Cavalieri R., Gupta P., Pass F., Shah K. V. Immunologic identification of papillomavirus antigen in condyloma tissues from the female genital tract. Obstet Gynecol. 1980 Dec;56(6):727–732. [PubMed] [Google Scholar]
  38. de Villiers E. M. Heterogeneity of the human papillomavirus group. J Virol. 1989 Nov;63(11):4898–4903. doi: 10.1128/jvi.63.11.4898-4903.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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