Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1993 Apr;67(4):1927–1935. doi: 10.1128/jvi.67.4.1927-1935.1993

Development of type-specific and cross-reactive serological probes for the minor capsid protein of human papillomavirus type 33.

C Volpers 1, M Sapp 1, C A Komly 1, P Richalet-Secordel 1, R E Streeck 1
PMCID: PMC240260  PMID: 8383218

Abstract

Human papillomavirus type 33 (HPV33) is associated with malignant tumors of the cervix. In an attempt to develop immunological probes for HPV33 infections, antisera against various bacterial fusion proteins carrying sequences of the minor capsid protein encoded by L2 were raised in animals. Antigenic determinants on the HPV33 L2 protein were identified by using truncated fusion proteins and were classified as type specific or cross-reactive with respect to HPV1, -8, -11, -16, and -18. Cross-reactive epitopes map to amino acids 98 to 107 or to amino acids 102 to 112 and 107 to 117, respectively, depending on the fusion protein used for immunization. Antibodies directed toward these epitopes detect L2 proteins of HPV11, -16, and -18, but not of HPV1 and -8, in Western immunoblots and enzyme-linked immunosorbent assays. HPV33 L2 amino acids 82 to 94 and 117 to 130 induce type-specific antibodies, with the major response directed to amino acids 117 to 130. By using a synthetic peptide corresponding to L2 amino acids 117 to 130, high-titered, type-specific antisera were obtained. These antisera should be useful as immunological probes for HPV33 infection.

Full text

PDF
1927

Images in this article

Selected References

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

  1. Beaudenon S., Kremsdorf D., Croissant O., Jablonska S., Wain-Hobson S., Orth G. A novel type of human papillomavirus associated with genital neoplasias. Nature. 1986 May 15;321(6067):246–249. doi: 10.1038/321246a0. [DOI] [PubMed] [Google Scholar]
  2. Beckmann A. M., Myerson D., Daling J. R., Kiviat N. B., Fenoglio C. M., McDougall J. K. Detection and localization of human papillomavirus DNA in human genital condylomas by in situ hybridization with biotinylated probes. J Med Virol. 1985 Jul;16(3):265–273. doi: 10.1002/jmv.1890160307. [DOI] [PubMed] [Google Scholar]
  3. Casadaban M. J., Martinez-Arias A., Shapira S. K., Chou J. Beta-galactosidase gene fusions for analyzing gene expression in escherichia coli and yeast. Methods Enzymol. 1983;100:293–308. doi: 10.1016/0076-6879(83)00063-4. [DOI] [PubMed] [Google Scholar]
  4. Cole S. T., Danos O. Nucleotide sequence and comparative analysis of the human papillomavirus type 18 genome. Phylogeny of papillomaviruses and repeated structure of the E6 and E7 gene products. J Mol Biol. 1987 Feb 20;193(4):599–608. doi: 10.1016/0022-2836(87)90343-3. [DOI] [PubMed] [Google Scholar]
  5. Cole S. T., Streeck R. E. Genome organization and nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer. J Virol. 1986 Jun;58(3):991–995. doi: 10.1128/jvi.58.3.991-995.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Crum C. P., Barber S., Symbula M., Snyder K., Saleh A. M., Roche J. K. Coexpression of the human papillomavirus type 16 E4 and L1 open reading frames in early cervical neoplasia. Virology. 1990 Sep;178(1):238–246. doi: 10.1016/0042-6822(90)90399-c. [DOI] [PubMed] [Google Scholar]
  8. Danos O., Katinka M., Yaniv M. Human papillomavirus 1a complete DNA sequence: a novel type of genome organization among papovaviridae. EMBO J. 1982;1(2):231–236. doi: 10.1002/j.1460-2075.1982.tb01152.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Dillner L., Heino P., Moreno-Lopez J., Dillner J. Antigenic and immunogenic epitopes shared by human papillomavirus type 16 and bovine, canine, and avian papillomaviruses. J Virol. 1991 Dec;65(12):6862–6871. doi: 10.1128/jvi.65.12.6862-6871.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Firzlaff J. M., Kiviat N. B., Beckmann A. M., Jenison S. A., Galloway D. A. Detection of human papillomavirus capsid antigens in various squamous epithelial lesions using antibodies directed against the L1 and L2 open reading frames. Virology. 1988 Jun;164(2):467–477. doi: 10.1016/0042-6822(88)90561-2. [DOI] [PubMed] [Google Scholar]
  13. Fuchs P. G., Iftner T., Weninger J., Pfister H. Epidermodysplasia verruciformis-associated human papillomavirus 8: genomic sequence and comparative analysis. J Virol. 1986 May;58(2):626–634. doi: 10.1128/jvi.58.2.626-634.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jenison S. A., Firzlaff J. M., Langenberg A., Galloway D. A. Identification of immunoreactive antigens of human papillomavirus type 6b by using Escherichia coli-expressed fusion proteins. J Virol. 1988 Jun;62(6):2115–2123. doi: 10.1128/jvi.62.6.2115-2123.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jenison S. A., Yu X. P., Valentine J. M., Galloway D. A. Characterization of human antibody-reactive epitopes encoded by human papillomavirus types 16 and 18. J Virol. 1991 Mar;65(3):1208–1218. doi: 10.1128/jvi.65.3.1208-1218.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Jenison S. A., Yu X. P., Valentine J. M., Koutsky L. A., Christiansen A. E., Beckmann A. M., Galloway D. A. Evidence of prevalent genital-type human papillomavirus infections in adults and children. J Infect Dis. 1990 Jul;162(1):60–69. doi: 10.1093/infdis/162.1.60. [DOI] [PubMed] [Google Scholar]
  18. Jenkins D., Tay S. K., McCance D. J., Campion M. J., Clarkson P. K., Singer A. Histological and immunocytochemical study of cervical intraepithelial neoplasia (CIN) with associated HPV 6 and HPV 16 infections. J Clin Pathol. 1986 Nov;39(11):1177–1180. doi: 10.1136/jcp.39.11.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jenson A. B., Kurman R. J., Lancaster W. D. Detection of papillomavirus common antigens in lesions of skin and mucosa. Clin Dermatol. 1985 Oct-Dec;3(4):56–63. doi: 10.1016/0738-081x(85)90049-5. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Jochmus-Kudielka I., Schneider A., Braun R., Kimmig R., Koldovsky U., Schneweis K. E., Seedorf K., Gissmann L. Antibodies against the human papillomavirus type 16 early proteins in human sera: correlation of anti-E7 reactivity with cervical cancer. J Natl Cancer Inst. 1989 Nov 15;81(22):1698–1704. doi: 10.1093/jnci/81.22.1698. [DOI] [PubMed] [Google Scholar]
  22. Kaur P., McDougall J. K. HPV-18 immortalization of human keratinocytes. Virology. 1989 Nov;173(1):302–310. doi: 10.1016/0042-6822(89)90247-x. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Köchel H. G., Monazahian M., Sievert K., Höhne M., Thomssen C., Teichmann A., Arendt P., Thomssen R. Occurrence of antibodies to L1, L2, E4 and E7 gene products of human papillomavirus types 6b, 16 and 18 among cervical cancer patients and controls. Int J Cancer. 1991 Jul 9;48(5):682–688. doi: 10.1002/ijc.2910480509. [DOI] [PubMed] [Google Scholar]
  26. Köchel H. G., Sievert K., Monazahian M., Mittelstädt-Deterding A., Teichmann A., Thomssen R. Antibodies to human papillomavirus type-16 in human sera as revealed by the use of prokaryotically expressed viral gene products. Virology. 1991 Jun;182(2):644–654. doi: 10.1016/0042-6822(91)90605-b. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Lancaster W. D., Kurman R. J., Sanz L. E., Perry S., Jenson A. B. Human papillomavirus: detection of viral DNA sequences and evidence for molecular heterogeneity in metaplasias and dysplasias of the uterine cervix. Intervirology. 1983;20(4):202–212. doi: 10.1159/000149393. [DOI] [PubMed] [Google Scholar]
  29. Lehtinen M., Parkkonen P., Niemelä J., Paavonen J. Demonstration of evolutionary differences between conserved antigenic epitopes in the minor nucleocapsid protein of human papillomavirus types 6b, 16 and 18. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1378–1383. doi: 10.1016/0006-291x(90)91602-o. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Lörincz A. T., Temple G. F., Patterson J. A., Jenson A. B., Kurman R. J., Lancaster W. D. Correlation of cellular atypia and human papillomavirus deoxyribonucleic acid sequences in exfoliated cells of the uterine cervix. Obstet Gynecol. 1986 Oct;68(4):508–512. [PubMed] [Google Scholar]
  32. Mandelson M. T., Jenison S. A., Sherman K. J., Valentine J. M., McKnight B., Daling J. R., Galloway D. A. The association of human papillomavirus antibodies with cervical cancer risk. Cancer Epidemiol Biomarkers Prev. 1992 May-Jun;1(4):281–286. [PubMed] [Google Scholar]
  33. 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]
  34. Nilsson B., Abrahmsén L., Uhlén M. Immobilization and purification of enzymes with staphylococcal protein A gene fusion vectors. EMBO J. 1985 Apr;4(4):1075–1080. doi: 10.1002/j.1460-2075.1985.tb03741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Oriel J. D., Almeida J. D. Demonstration of virus particles in human genital warts. Br J Vener Dis. 1970 Feb;46(1):37–42. doi: 10.1136/sti.46.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Pecoraro G., Morgan D., Defendi V. Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells. Proc Natl Acad Sci U S A. 1989 Jan;86(2):563–567. doi: 10.1073/pnas.86.2.563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pyrhönen S. Hunan wart-virus antibodies in patients with genital and skin warts. Acta Derm Venereol. 1978;58(5):427–432. [PubMed] [Google Scholar]
  39. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  40. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  43. Stacey S. N., Bartholomew J. S., Ghosh A., Stern P. L., Mackett M., Arrand J. R. Expression of human papillomavirus type 16 E6 protein by recombinant baculovirus and use for detection of anti-E6 antibodies in human sera. J Gen Virol. 1992 Sep;73(Pt 9):2337–2345. doi: 10.1099/0022-1317-73-9-2337. [DOI] [PubMed] [Google Scholar]
  44. Storey A., Pim D., Murray A., Osborn K., Banks L., Crawford L. Comparison of the in vitro transforming activities of human papillomavirus types. EMBO J. 1988 Jun;7(6):1815–1820. doi: 10.1002/j.1460-2075.1988.tb03013.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Tagami H., Oguchi M., Ofuji S. Immunological aspects of wart regression with special reference to regression phenomenon of numerous flat warts. An experiment on tumor immunity in man by nature. J Dermatol. 1983 Feb;10(1):1–12. doi: 10.1111/j.1346-8138.1983.tb01098.x. [DOI] [PubMed] [Google Scholar]
  47. Tidy J. A., Parry G. C., Ward P., Coleman D. V., Peto J., Malcolm A. D., Farrell P. J. High rate of human papillomavirus type 16 infection in cytologically normal cervices. Lancet. 1989 Feb 25;1(8635):434–434. doi: 10.1016/s0140-6736(89)90023-8. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ullmann A. One-step purification of hybrid proteins which have beta-galactosidase activity. Gene. 1984 Jul-Aug;29(1-2):27–31. doi: 10.1016/0378-1119(84)90162-8. [DOI] [PubMed] [Google Scholar]
  52. Wickenden C., Steele A., Malcolm A. D., Coleman D. V. Screening for wart virus infection in normal and abnormal cervices by DNA hybridisation of cervical scrapes. Lancet. 1985 Jan 12;1(8420):65–67. doi: 10.1016/s0140-6736(85)91963-4. [DOI] [PubMed] [Google Scholar]
  53. 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]
  54. Yaegashi N., Jenison S. A., Batra M., Galloway D. A. Human antibodies recognize multiple distinct type-specific and cross-reactive regions of the minor capsid proteins of human papillomavirus types 6 and 11. J Virol. 1992 Apr;66(4):2008–2019. doi: 10.1128/jvi.66.4.2008-2019.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Yasumoto S., Burkhardt A. L., Doniger J., DiPaolo J. A. Human papillomavirus type 16 DNA-induced malignant transformation of NIH 3T3 cells. J Virol. 1986 Feb;57(2):572–577. doi: 10.1128/jvi.57.2.572-577.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Young L. S., Bevan I. S., Johnson M. A., Blomfield P. I., Bromidge T., Maitland N. J., Woodman C. B. The polymerase chain reaction: a new epidemiological tool for investigating cervical human papillomavirus infection. BMJ. 1989 Jan 7;298(6665):14–18. doi: 10.1136/bmj.298.6665.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. 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]
  58. de Villiers E. M., Wagner D., Schneider A., Wesch H., Miklaw H., Wahrendorf J., Papendick U., zur Hausen H. Human papillomavirus infections in women with and without abnormal cervical cytology. Lancet. 1987 Sep 26;2(8561):703–706. doi: 10.1016/s0140-6736(87)91072-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES