Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Feb;69(2):948–954. doi: 10.1128/jvi.69.2.948-954.1995

Papillomavirus capsid binding and uptake by cells from different tissues and species.

M Müller 1, L Gissmann 1, R J Cristiano 1, X Y Sun 1, I H Frazer 1, A B Jenson 1, A Alonso 1, H Zentgraf 1, J Zhou 1
PMCID: PMC188663  PMID: 7815562

Abstract

The inability of papillomaviruses (PV) to replicate in tissue culture cells has hampered the study of the PV life cycle. We investigated virus-cell interactions by the following two methods: (i) using purified bovine PV virions or human PV type 11 (HPV type 11) virus-like particles (VLP) to test the binding to eukaryotic cells and (ii) using different VLP-reporter plasmid complexes of HPV6b, HPV11 L1 or HPV11 L1/L2, and HPV16 L1 or HPV16 L1/L2 to study uptake of particles into different cell lines. Our studies showed that PV capsids bind to a broad range of cells in culture in a dose-dependent manner. Binding of PV capsids to cells can be blocked by pretreating the cells with the protease trypsin. Penetration of PV into cells was monitored by using complexes in which the purified PV capsids were physically linked to DNA containing the gene for beta-galactosidase driven by the human cytomegalovirus promoter. Expression of beta-galactosidase occurred in < 1% of the cells, and the efficiency of PV receptor-mediated gene delivery was greatly enhanced (up to 10 to 20% positive cells) by the use of a replication-defective adenovirus which promotes endosomal lysis. The data generated by this approach further confirmed the results obtained from the binding assays, showing that PV enter a wide range of cells and that these cells have all functions required for the uptake of PV. Binding and uptake of PV particles can be blocked by PV-specific antisera, and different PV particles compete for particle uptake. Our results suggest that the PV receptor is a conserved cell surface molecule(s) used by different PV and that the tropism of infection by different PV is controlled by events downstream of the initial binding and uptake.

Full Text

The Full Text of this article is available as a PDF (540.8 KB).

Selected References

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

  1. Baker T. S., Newcomb W. W., Olson N. H., Cowsert L. M., Olson C., Brown J. C. Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J. 1991 Dec;60(6):1445–1456. doi: 10.1016/S0006-3495(91)82181-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Collins A. R. HLA class I antigen serves as a receptor for human coronavirus OC43. Immunol Invest. 1993 Mar;22(2):95–103. doi: 10.3109/08820139309063393. [DOI] [PubMed] [Google Scholar]
  4. Cotten M., Längle-Rouault F., Kirlappos H., Wagner E., Mechtler K., Zenke M., Beug H., Birnstiel M. L. Transferrin-polycation-mediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4033–4037. doi: 10.1073/pnas.87.11.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cowsert L. M., Pilacinski W. P., Jenson A. B. Identification of the bovine papillomavirus L1 gene product using monoclonal antibodies. Virology. 1988 Aug;165(2):613–615. doi: 10.1016/0042-6822(88)90608-3. [DOI] [PubMed] [Google Scholar]
  6. Cristiano R. J., Smith L. C., Kay M. A., Brinkley B. R., Woo S. L. Hepatic gene therapy: efficient gene delivery and expression in primary hepatocytes utilizing a conjugated adenovirus-DNA complex. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11548–11552. doi: 10.1073/pnas.90.24.11548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cristiano R. J., Smith L. C., Woo S. L. Hepatic gene therapy: adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2122–2126. doi: 10.1073/pnas.90.6.2122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dollard S. C., Wilson J. L., Demeter L. M., Bonnez W., Reichman R. C., Broker T. R., Chow L. T. Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. OFF. Genes Dev. 1992 Jul;6(7):1131–1142. doi: 10.1101/gad.6.7.1131. [DOI] [PubMed] [Google Scholar]
  9. Doorbar J., Gallimore P. H. Identification of proteins encoded by the L1 and L2 open reading frames of human papillomavirus 1a. J Virol. 1987 Sep;61(9):2793–2799. doi: 10.1128/jvi.61.9.2793-2799.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dürst M., Glitz D., Schneider A., zur Hausen H. Human papillomavirus type 16 (HPV 16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology. 1992 Jul;189(1):132–140. doi: 10.1016/0042-6822(92)90688-l. [DOI] [PubMed] [Google Scholar]
  11. Fantini J., Cook D. G., Nathanson N., Spitalnik S. L., Gonzalez-Scarano F. Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2700–2704. doi: 10.1073/pnas.90.7.2700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Favre M. Structural polypeptides of rabbit, bovine, and human papillomaviruses. J Virol. 1975 May;15(5):1239–1247. doi: 10.1128/jvi.15.5.1239-1247.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gissmann L., Pfister H., Zur Hausen H. Human papilloma viruses (HPV): characterization of four different isolates. Virology. 1977 Feb;76(2):569–580. doi: 10.1016/0042-6822(77)90239-2. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Keppler O. T., Herrmann M., Oppenländer M., Meschede W., Pawlita M. Regulation of susceptibility and cell surface receptor for the B-lymphotropic papovavirus by N glycosylation. J Virol. 1994 Nov;68(11):6933–6939. doi: 10.1128/jvi.68.11.6933-6939.1994. [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. 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]
  19. Lancaster W. D., Olson C. Animal papillomaviruses. Microbiol Rev. 1982 Jun;46(2):191–207. doi: 10.1128/mr.46.2.191-207.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lancaster W. D., Olson C., Meinke W. Bovine papilloma virus: presence of virus-specific DNA sequences in naturally occurring equine tumors. Proc Natl Acad Sci U S A. 1977 Feb;74(2):524–528. doi: 10.1073/pnas.74.2.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lancaster W. D., Olson C., Meinke W. Quantitation of bovine papilloma viral DNA in viral-induced tumors. J Virol. 1976 Mar;17(3):824–831. doi: 10.1128/jvi.17.3.824-831.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nomoto A., Koike S., Aoki J. Tissue tropism and species specificity of poliovirus infection. Trends Microbiol. 1994 Feb;2(2):47–51. doi: 10.1016/0966-842x(94)90125-2. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Roden R. B., Weissinger E. M., Henderson D. W., Booy F., Kirnbauer R., Mushinski J. F., Lowy D. R., Schiller J. T. Neutralization of bovine papillomavirus by antibodies to L1 and L2 capsid proteins. J Virol. 1994 Nov;68(11):7570–7574. doi: 10.1128/jvi.68.11.7570-7574.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Sattentau Q. J., Weiss R. A. The CD4 antigen: physiological ligand and HIV receptor. Cell. 1988 Mar 11;52(5):631–633. doi: 10.1016/0092-8674(88)90397-2. [DOI] [PubMed] [Google Scholar]
  27. Signoret N., Poignard P., Blanc D., Sattentau Q. J. Human and simian immunodeficiency viruses: virus-receptor interactions. Trends Microbiol. 1993 Dec;1(9):328–333. doi: 10.1016/0966-842x(93)90072-y. [DOI] [PubMed] [Google Scholar]
  28. Taichman L. B., Breitburd F., Croissant O., Orth G. The search for a culture system for papillomavirus. J Invest Dermatol. 1984 Jul;83(1 Suppl):2s–6s. doi: 10.1111/1523-1747.ep12281108. [DOI] [PubMed] [Google Scholar]
  29. Tardieu M., Epstein R. L., Weiner H. L. Interaction of viruses with cell surface receptors. Int Rev Cytol. 1982;80:27–61. doi: 10.1016/S0074-7696(08)60366-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Wagner E., Zenke M., Cotten M., Beug H., Birnstiel M. L. Transferrin-polycation conjugates as carriers for DNA uptake into cells. Proc Natl Acad Sci U S A. 1990 May;87(9):3410–3414. doi: 10.1073/pnas.87.9.3410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wickham T. J., Mathias P., Cheresh D. A., Nemerow G. R. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell. 1993 Apr 23;73(2):309–319. doi: 10.1016/0092-8674(93)90231-e. [DOI] [PubMed] [Google Scholar]
  33. Zhou J., Stenzel D. J., Sun X. Y., Frazer I. H. Synthesis and assembly of infectious bovine papillomavirus particles in vitro. J Gen Virol. 1993 Apr;74(Pt 4):763–768. doi: 10.1099/0022-1317-74-4-763. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. zur Hausen H. Human papillomaviruses in the pathogenesis of anogenital cancer. Virology. 1991 Sep;184(1):9–13. doi: 10.1016/0042-6822(91)90816-t. [DOI] [PubMed] [Google Scholar]

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

RESOURCES