Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Nov 1994; 68(11): 7260–7266.
PMCID: PMC237166

Interaction of papillomaviruses with the cell surface.


To initiate an investigation of the initial step in papillomavirus infection, we have examined the interaction of bovine papillomavirus type 1 (BPV) virions with C127 cells by two assays, binding of radioiodinated BPV virions to cell monolayers and BPV-induced focal transformation. Under physiological conditions, the labeled virions bound to the cell surface in a dose-dependent manner within 1 h. Antibody studies indicated that the interaction was specific and related to infectivity: polyclonal sera raised to BPV virions or to baculovirus-expressed BPV L1 virus-like particles (VLPs) inhibited BPV binding and focal transformation, while sera to denatured BPV virions, to denatured BPV L1, or to human papillomavirus type 16 (HPV-16) VLPs were not inhibitory. An exception was that antisera to BPV L2 were neutralizing but did not inhibit binding. Unlabeled BPV virions and BPV VLPs competed with binding to the cell surface in a concentration-dependent manner. Binding to the cell surface appeared to depend primarily on L1, since BPV VLPs composed of L1 alone or of L1/L2 were equally effective in inhibiting binding and focal transformation. VLPs of HPV-16 also inhibited BPV binding and BPV transformation of C127 cells, suggesting that they interact with the same cell surface molecule(s) as BPV virions. Radiolabeled BPV bound specifically to several mammalian cell lines of fibroblastic and epithelial origin, as well as to a human schwannoma and melanoma lines, although some lines bound up to 10 times as many counts as others. Radiolabeled HPV-16 VLPs bound to both human keratinocytes and mouse C127 cells. The results suggest that papillomaviruses bind a widely expressed and evolutionarily conserved cell surface receptor.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baker TS, Newcomb WW, Olson NH, Cowsert LM, Olson C, Brown JC. Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J. 1991 Dec;60(6):1445–1456. [PMC free article] [PubMed]
  • Barbosa MS, Vass WC, Lowy DR, Schiller JT. In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential. J Virol. 1991 Jan;65(1):292–298. [PMC free article] [PubMed]
  • Bolton AE, Hunter WM. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. [PMC free article] [PubMed]
  • Cason J, Khan SA, Best JM. Towards vaccines against human papillomavirus type-16 genital infections. Vaccine. 1993;11(6):603–611. [PubMed]
  • Christensen ND, Kreider JW. Antibody-mediated neutralization in vivo of infectious papillomaviruses. J Virol. 1990 Jul;64(7):3151–3156. [PMC free article] [PubMed]
  • Christensen ND, Kreider JW. Monoclonal antibody neutralization of BPV-1. Virus Res. 1993 May;28(2):195–202. [PubMed]
  • Christensen ND, Kreider JW, Cladel NM, Patrick SD, Welsh PA. Monoclonal antibody-mediated neutralization of infectious human papillomavirus type 11. J Virol. 1990 Nov;64(11):5678–5681. [PMC free article] [PubMed]
  • Christensen ND, Kreider JW, Kan NC, DiAngelo SL. The open reading frame L2 of cottontail rabbit papillomavirus contains antibody-inducing neutralizing epitopes. Virology. 1991 Apr;181(2):572–579. [PubMed]
  • Compton T, Nowlin DM, Cooper NR. Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate. Virology. 1993 Apr;193(2):834–841. [PubMed]
  • Crawford L. Prospects for cervical cancer vaccines. Cancer Surv. 1993;16:215–229. [PubMed]
  • Dollard SC, Wilson JL, Demeter LM, Bonnez W, Reichman RC, Broker TR, Chow LT. Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. OFF. Genes Dev. 1992 Jul;6(7):1131–1142. [PubMed]
  • Dvoretzky I, Shober R, Chattopadhyay SK, Lowy DR. A quantitative in vitro focus assay for bovine papilloma virus. Virology. 1980 Jun;103(2):369–375. [PubMed]
  • Fletcher JA, Kozakewich HP, Hoffer FA, Lage JM, Weidner N, Tepper R, Pinkus GS, Morton CC, Corson JM. Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N Engl J Med. 1991 Feb 14;324(7):436–442. [PubMed]
  • Fraker PJ, Speck JC., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. [PubMed]
  • Fried H, Cahan LD, Paulson JC. Polyoma virus recognizes specific sialyligosaccharide receptors on host cells. Virology. 1981 Feb;109(1):188–192. [PubMed]
  • Ghim S, Christensen ND, Kreider JW, Jenson AB. Comparison of neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts. Int J Cancer. 1991 Sep 9;49(2):285–289. [PubMed]
  • Hagensee ME, Yaegashi N, Galloway DA. 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. [PMC free article] [PubMed]
  • Haywood AM. Virus receptors: binding, adhesion strengthening, and changes in viral structure. J Virol. 1994 Jan;68(1):1–5. [PMC free article] [PubMed]
  • Iwasawa A, Kumamoto Y, Fujinaga K. Detection of human papillomavirus deoxyribonucleic acid in penile carcinoma by polymerase chain reaction and in situ hybridization. J Urol. 1993 Jan;149(1):59–63. [PubMed]
  • Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT. 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. [PMC free article] [PubMed]
  • Kirnbauer R, Hubbert NL, Wheeler CM, Becker TM, Lowy DR, Schiller JT. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst. 1994 Apr 6;86(7):494–499. [PMC free article] [PubMed]
  • Kirnbauer R, Taub J, Greenstone H, Roden R, Dürst M, Gissmann L, Lowy DR, Schiller JT. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J Virol. 1993 Dec;67(12):6929–6936. [PMC free article] [PubMed]
  • Koller LD, Olson C. Attempted transmission of warts from man, cattle, and horses and of deer fibroma, to selected hosts. J Invest Dermatol. 1972 Jun;58(6):366–368. [PubMed]
  • Koutsky LA, Holmes KK, Critchlow CW, Stevens CE, Paavonen J, Beckmann AM, DeRouen TA, Galloway DA, Vernon D, Kiviat NB. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med. 1992 Oct 29;327(18):1272–1278. [PubMed]
  • Kreider JW, Howett MK, Leure-Dupree AE, Zaino RJ, Weber JA. Laboratory production in vivo of infectious human papillomavirus type 11. J Virol. 1987 Feb;61(2):590–593. [PMC free article] [PubMed]
  • Lancaster WD, Meinke W. Persistence of viral DNA in human cell cultures infected with human papilloma virus. Nature. 1975 Jul 31;256(5516):434–436. [PubMed]
  • Lin YL, Borenstein LA, Selvakumar R, Ahmed R, Wettstein FO. Effective vaccination against papilloma development by immunization with L1 or L2 structural protein of cottontail rabbit papillomavirus. Virology. 1992 Apr;187(2):612–619. [PubMed]
  • Meyers C, Frattini MG, Hudson JB, Laimins LA. Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation. Science. 1992 Aug 14;257(5072):971–973. [PubMed]
  • Larsen PM, Storgaard L, Fey SJ. Proteins present in bovine papillomavirus particles. J Virol. 1987 Nov;61(11):3596–3601. [PMC free article] [PubMed]
  • Robl MG, Gordon DE, Lee KP, Olson C. Intracranial fibroblastic neoplasms in the hamster from bovine papilloma virus. Cancer Res. 1972 Oct;32(10):2221–2225. [PubMed]
  • Rose RC, Bonnez W, Reichman RC, Garcea RL. 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. [PMC free article] [PubMed]
  • Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, Scott DR, Sherman ME, Kurman RJ, Wacholder S, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst. 1993 Jun 16;85(12):958–964. [PubMed]
  • SEGRE D, OLSON C, Jr, HOERLEIN AB. Neutralization of bovine papilloma virus with serums from cattle and horses with experimental papillomas. Am J Vet Res. 1955 Oct;16(61 Pt 1):517–520. [PubMed]
  • Shieh MT, WuDunn D, Montgomery RI, Esko JD, Spear PG. Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. J Cell Biol. 1992 Mar;116(5):1273–1281. [PMC free article] [PubMed]
  • Smith LH, Foster C, Hitchcock ME, Isseroff R. In vitro HPV-11 infection of human foreskin. J Invest Dermatol. 1993 Sep;101(3):292–295. [PubMed]
  • Steinberg BM, Auborn KJ, Brandsma JL, Taichman LB. Tissue site-specific enhancer function of the upstream regulatory region of human papillomavirus type 11 in cultured keratinocytes. J Virol. 1989 Feb;63(2):957–960. [PMC free article] [PubMed]
  • White JM, Littman DR. Viral receptors of the immunoglobulin superfamily. Cell. 1989 Mar 10;56(5):725–728. [PubMed]
  • Zhou J, Stenzel DJ, Sun XY, Frazer IH. Synthesis and assembly of infectious bovine papillomavirus particles in vitro. J Gen Virol. 1993 Apr;74(Pt 4):763–768. [PubMed]

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


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...