Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Jul;70(7):4791–4794. doi: 10.1128/jvi.70.7.4791-4794.1996

Two amino acid residues confer type specificity to a neutralizing, conformationally dependent epitope on human papillomavirus type 11.

S W Ludmerer 1, D Benincasa 1, G E Mark 3rd 1
PMCID: PMC190419  PMID: 8676509

Abstract

Characterization of virus binding by neutralizing antibodies is important both in understanding early events in viral infectivity and in development of vaccines. Neutralizing monoclonal antibodies (MAbs) to human papillomavirus type 11 (HPV11) have been described, but mapping the binding site has been difficult because of the conformational nature of key type-specific neutralization epitopes on the L1 coat protein. We have determined those residues of the L1 protein of HPV11 which confer type specificity to the binding of HPV11-neutralizing MAbs. Binding of three HPV11-specific neutralizing MAbs could be redirected to HPV6 L1 virus-like particles in which as few as two substitutions of corresponding amino acid residues from HPV11 L1 have been made, thus demonstrating the importance of these residues to MAb binding through the transfer of a conformationally dependent epitope. In addition, a fourth neutralizing MAb could be distinguished from the other neutralizing MAbs in terms of the amino acid residues which affect binding, suggesting the possibility that it neutralizes HPV11 through a different mechanism.

Full Text

The Full Text of this article is available as a PDF (281.8 KB).

Selected References

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

  1. Benincasa D., Silberklang M., Mark G. E., 3rd, Ludmerer S. W. Rapid, high-level transient expression of papillomavirus-like particles in insect cells. Biotechniques. 1996 May;20(5):890–895. doi: 10.2144/96205rr02. [DOI] [PubMed] [Google Scholar]
  2. Christensen N. D., Höpfl R., DiAngelo S. L., Cladel N. M., Patrick S. D., Welsh P. A., Budgeon L. R., Reed C. A., Kreider J. W. Assembled baculovirus-expressed human papillomavirus type 11 L1 capsid protein virus-like particles are recognized by neutralizing monoclonal antibodies and induce high titres of neutralizing antibodies. J Gen Virol. 1994 Sep;75(Pt 9):2271–2276. doi: 10.1099/0022-1317-75-9-2271. [DOI] [PubMed] [Google Scholar]
  3. Christensen N. D., Kirnbauer R., Schiller J. T., Ghim S. J., Schlegel R., Jenson A. B., Kreider J. W. Human papillomavirus types 6 and 11 have antigenically distinct strongly immunogenic conformationally dependent neutralizing epitopes. Virology. 1994 Nov 15;205(1):329–335. doi: 10.1006/viro.1994.1649. [DOI] [PubMed] [Google Scholar]
  4. Christensen N. D., Kreider J. W. Antibody-mediated neutralization in vivo of infectious papillomaviruses. J Virol. 1990 Jul;64(7):3151–3156. doi: 10.1128/jvi.64.7.3151-3156.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christensen N. D., Kreider J. W., Cladel N. M., Patrick S. D., Welsh P. A. Monoclonal antibody-mediated neutralization of infectious human papillomavirus type 11. J Virol. 1990 Nov;64(11):5678–5681. doi: 10.1128/jvi.64.11.5678-5681.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Christensen N. D., Kreider J. W. Neutralization of CRPV infectivity by monoclonal antibodies that identify conformational epitopes on intact virions. Virus Res. 1991 Nov;21(3):169–179. doi: 10.1016/0168-1702(91)90031-p. [DOI] [PubMed] [Google Scholar]
  7. Christensen N. D., Reed C. A., Cladel N. M. Induction of neutralizing antibodies to papillomaviruses by anti-idiotypic antibodies. Virology. 1995 Jul 10;210(2):292–301. doi: 10.1006/viro.1995.1346. [DOI] [PubMed] [Google Scholar]
  8. Dartmann K., Schwarz E., Gissmann L., zur Hausen H. The nucleotide sequence and genome organization of human papilloma virus type 11. Virology. 1986 May;151(1):124–130. doi: 10.1016/0042-6822(86)90110-8. [DOI] [PubMed] [Google Scholar]
  9. Galloway D. A. Human papillomavirus vaccines: a warty problem. Infect Agents Dis. 1994 Aug;3(4):187–193. [PubMed] [Google Scholar]
  10. Hagensee M. E., Yaegashi N., Galloway D. A. Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the L1 and L2 capsid proteins. J Virol. 1993 Jan;67(1):315–322. doi: 10.1128/jvi.67.1.315-322.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hofmann K. J., Cook J. C., Joyce J. G., Brown D. R., Schultz L. D., George H. A., Rosolowsky M., Fife K. H., Jansen K. U. Sequence determination of human papillomavirus type 6a and assembly of virus-like particles in Saccharomyces cerevisiae. Virology. 1995 Jun 1;209(2):506–518. doi: 10.1006/viro.1995.1283. [DOI] [PubMed] [Google Scholar]
  12. Jarrett W. F., O'Neil B. W., Gaukroger J. M., Laird H. M., Smith K. T., Campo M. S. Studies on vaccination against papillomaviruses: a comparison of purified virus, tumour extract and transformed cells in prophylactic vaccination. Vet Rec. 1990 May 5;126(18):449–452. [PubMed] [Google Scholar]
  13. Jarrett W. F., O'Neil B. W., Gaukroger J. M., Smith K. T., Laird H. M., Campo M. S. Studies on vaccination against papillomaviruses: the immunity after infection and vaccination with bovine papillomaviruses of different types. Vet Rec. 1990 May 12;126(19):473–475. [PubMed] [Google Scholar]
  14. Jarrett W. F., Smith K. T., O'Neil B. W., Gaukroger J. M., Chandrachud L. M., Grindlay G. J., McGarvie G. M., Campo M. S. Studies on vaccination against papillomaviruses: prophylactic and therapeutic vaccination with recombinant structural proteins. Virology. 1991 Sep;184(1):33–42. doi: 10.1016/0042-6822(91)90819-w. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kirnbauer R., Booy F., Cheng N., Lowy D. R., Schiller J. T. Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12180–12184. doi: 10.1073/pnas.89.24.12180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kirnbauer R., Taub J., Greenstone H., Roden R., Dürst M., Gissmann L., Lowy D. R., Schiller J. T. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J Virol. 1993 Dec;67(12):6929–6936. doi: 10.1128/jvi.67.12.6929-6936.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kreider J. W., Howett M. K., Wolfe S. A., Bartlett G. L., Zaino R. J., Sedlacek T., Mortel R. Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata. Nature. 1985 Oct 17;317(6038):639–641. doi: 10.1038/317639a0. [DOI] [PubMed] [Google Scholar]
  19. Muggeridge M. I., Wu T. T., Johnson D. C., Glorioso J. C., Eisenberg R. J., Cohen G. H. Antigenic and functional analysis of a neutralization site of HSV-1 glycoprotein D. Virology. 1990 Feb;174(2):375–387. doi: 10.1016/0042-6822(90)90091-5. [DOI] [PubMed] [Google Scholar]
  20. Roden R. B., Kirnbauer R., Jenson A. B., Lowy D. R., Schiller J. T. Interaction of papillomaviruses with the cell surface. J Virol. 1994 Nov;68(11):7260–7266. doi: 10.1128/jvi.68.11.7260-7266.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rose R. C., Bonnez W., Reichman R. C., Garcea R. L. Expression of human papillomavirus type 11 L1 protein in insect cells: in vivo and in vitro assembly of viruslike particles. J Virol. 1993 Apr;67(4):1936–1944. doi: 10.1128/jvi.67.4.1936-1944.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schwarz E., Dürst M., Demankowski C., Lattermann O., Zech R., Wolfsperger E., Suhai S., zur Hausen H. DNA sequence and genome organization of genital human papillomavirus type 6b. EMBO J. 1983;2(12):2341–2348. doi: 10.1002/j.1460-2075.1983.tb01744.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zhou J., Sun X. Y., Stenzel D. J., Frazer I. H. Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology. 1991 Nov;185(1):251–257. doi: 10.1016/0042-6822(91)90772-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES