1887

Abstract

Oncogenic human papillomaviruses (HPVs) attach predominantly to extracellular matrix (ECM) components during infection of cultured keratinocytes and in the rodent vaginal challenge model . However, the mechanism of virion transfer from the ECM to receptors that mediate entry into host cells has not been determined. In this work we strove to assess the role of heparan sulfate (HS) chains in HPV16 binding to the ECM and determine how HPV16 release from the ECM is regulated. We also assessed the extent to which capsids released from the ECM are infectious. We show that a large fraction of HPV16 particles binds to the ECM via HS chains, and that syndecan-1 (snd-1) molecules present in the ECM are involved in virus binding. Inhibiting the normal processing of snd-1 and HS molecules via matrix metalloproteinases and heparanase dramatically reduces virus release from the ECM, cellular uptake and infection. Conversely, exogenous heparinase activates each of these processes. We confirm that HPV16 released from the ECM is infectious in keratinocytes. Use of a specific inhibitor shows furin is not involved in HPV16 release from ECM attachment factors and corroborates other studies showing only the intracellular activity of furin is responsible for modulating HPV infectivity. These data suggest that our recently proposed model, describing the action of HS proteoglycan processing enzymes in releasing HPV16 from the cell surface in complex with the attachment factor snd-1, is also relevant to the release of HPV16 particles from the ECM to promote efficient infection of keratinocytes.

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2015-08-01
2019-10-19
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References

  1. Bayer-Garner I.B., Sanderson R.D., Dhodapkar M.V., Owens R.B., Wilson C.S.. ( 2001;). Syndecan-1 (CD138) immunoreactivity in bone marrow biopsies of multiple myeloma: shed syndecan-1 accumulates in fibrotic regions. Mod Pathol 14: 1052–1058 [CrossRef] [PubMed].
    [Google Scholar]
  2. Bernfield M., Götte M., Park P.W., Reizes O., Fitzgerald M.L., Lincecum J., Zako M.. ( 1999;). Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 68: 729–777 [CrossRef] [PubMed].
    [Google Scholar]
  3. Bishop J.R., Schuksz M., Esko J.D.. ( 2007;). Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446: 1030–1037 [CrossRef] [PubMed].
    [Google Scholar]
  4. Burkard C., Bloyet L.-M., Wicht O., van Kuppeveld F.J., Rottier P.J.M., de Haan C.A.M., Bosch B.J.. ( 2014;). Dissecting virus entry: replication-independent analysis of virus binding, internalization, and penetration using minimal complementation of β-galactosidase. PLoS One 9: e101762 [CrossRef] [PubMed].
    [Google Scholar]
  5. Campos S.K., Ozbun M.A.. ( 2009;). Two highly conserved cysteine residues in HPV16 L2 form an intramolecular disulfide bond and are critical for infectivity in human keratinocytes. PLoS One 4: e4463 [CrossRef] [PubMed].
    [Google Scholar]
  6. Campos S.K., Chapman J.A., Deymier M.J., Bronnimann M.P., Ozbun M.A.. ( 2012;). Opposing effects of bacitracin on human papillomavirus type 16 infection: enhancement of binding and entry and inhibition of endosomal penetration. J Virol 86: 4169–4181 [CrossRef] [PubMed].
    [Google Scholar]
  7. Carulli S., Beck K., Dayan G., Boulesteix S., Lortat-Jacob H., Rousselle P.. ( 2012;). Cell surface proteoglycans syndecan-1 and -4 bind overlapping but distinct sites in laminin α3 LG45 protein domain. J Biol Chem 287: 12204–12216 [CrossRef] [PubMed].
    [Google Scholar]
  8. Cerqueira C., Liu Y., Kühling L., Chai W., Hafezi W., van Kuppevelt T.H., Kühn J.E., Feizi T., Schelhaas M.. ( 2013;). Heparin increases the infectivity of Human Papillomavirus type 16 independent of cell surface proteoglycans and induces L1 epitope exposure. Cell Microbiol 15: 1818–1836 [PubMed].
    [Google Scholar]
  9. Chesson H.W., Ekwueme D.U., Saraiya M., Watson M., Lowy D.R., Markowitz L.E.. ( 2012;). Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. Vaccine 30: 6016–6019 [CrossRef] [PubMed].
    [Google Scholar]
  10. Choi S., Lee H., Choi J.R., Oh E.S.. ( 2010;). Shedding; towards a new paradigm of syndecan function in cancer. BMB Rep 43: 305–310 [CrossRef] [PubMed].
    [Google Scholar]
  11. Choi Y., Chung H., Jung H., Couchman J.R., Oh E.-S.. ( 2011;). Syndecans as cell surface receptors: unique structure equates with functional diversity. Matrix Biol 30: 93–99 [CrossRef] [PubMed].
    [Google Scholar]
  12. Combita A.L., Touzé A., Bousarghin L., Sizaret P.-Y., Muñoz N., Coursaget P.. ( 2001;). Gene transfer using human papillomavirus pseudovirions varies according to virus genotype and requires cell surface heparan sulfate. FEMS Microbiol Lett 204: 183–188 [CrossRef] [PubMed].
    [Google Scholar]
  13. Culp T.D., Budgeon L.R., Christensen N.D.. ( 2006a;). Human papillomaviruses bind a basal extracellular matrix component secreted by keratinocytes which is distinct from a membrane-associated receptor. Virology 347: 147–159 [CrossRef] [PubMed].
    [Google Scholar]
  14. Culp T.D., Budgeon L.R., Marinkovich M.P., Meneguzzi G., Christensen N.D.. ( 2006b;). Keratinocyte-secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells. J Virol 80: 8940–8950 [CrossRef] [PubMed].
    [Google Scholar]
  15. Dasgupta J., Bienkowska-Haba M., Ortega M.E., Patel H.D., Bodevin S., Spillmann D., Bishop B., Sapp M., Chen X.S.. ( 2011;). Structural basis of oligosaccharide receptor recognition by human papillomavirus. J Biol Chem 286: 2617–2624 [CrossRef] [PubMed].
    [Google Scholar]
  16. Day P.M., Schelhaas M.. ( 2014;). Concepts of papillomavirus entry into host cells. Curr Opin Virol 4: 24–31 [CrossRef] [PubMed].
    [Google Scholar]
  17. Day P.M., Thompson C.D., Buck C.B., Pang Y.Y., Lowy D.R., Schiller J.T.. ( 2007;). Neutralization of human papillomavirus with monoclonal antibodies reveals different mechanisms of inhibition. J Virol 81: 8784–8792 [CrossRef] [PubMed].
    [Google Scholar]
  18. Day P.M., Gambhira R., Roden R.B., Lowy D.R., Schiller J.T.. ( 2008;). Mechanisms of human papillomavirus type 16 neutralization by l2 cross-neutralizing and l1 type-specific antibodies. J Virol 82: 4638–4646 [CrossRef] [PubMed].
    [Google Scholar]
  19. Ding K., Lopez-Burks M., Sánchez-Duran J.A., Korc M., Lander A.D.. ( 2005;). Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J Cell Biol 171: 729–738 [CrossRef] [PubMed].
    [Google Scholar]
  20. Elenius K., Jalkanen M.. ( 1994;). Function of the syndecans - a family of cell surface proteoglycans. J Cell Sci 107: 2975–2982 [PubMed].
    [Google Scholar]
  21. Elkin M., Ilan N., Ishai-Michaeli R., Friedmann Y., Papo O., Pecker I., Vlodavsky I.. ( 2001;). Heparanase as mediator of angiogenesis: mode of action. FASEB J 15: 1661–1663 [PubMed].
    [Google Scholar]
  22. Faust H., Knekt P., Forslund O., Dillner J.. ( 2010;). Validation of multiplexed human papillomavirus serology using pseudovirions bound to heparin-coated beads. J Gen Virol 91: 1840–1848 [CrossRef] [PubMed].
    [Google Scholar]
  23. Fears C.Y., Woods A.. ( 2006;). The role of syndecans in disease and wound healing. Matrix Biol 25: 443–456 [CrossRef] [PubMed].
    [Google Scholar]
  24. Flannery C.R.. ( 2006;). MMPs and ADAMTSs: functional studies. Front Biosci 11: 544–569 [CrossRef] [PubMed].
    [Google Scholar]
  25. Forman D., de Martel C., Lacey C.J., Soerjomataram I., Lortet-Tieulent J., Bruni L., Vignat J., Ferlay J., Bray F., other authors. ( 2012;). Global burden of human papillomavirus and related diseases. Vaccine 30: (Suppl 5), F12–F23 [CrossRef] [PubMed].
    [Google Scholar]
  26. Giroglou T., Florin L., Schäfer F., Streeck R.E., Sapp M.. ( 2001;). Human papillomavirus infection requires cell surface heparan sulfate. J Virol 75: 1565–1570 [CrossRef] [PubMed].
    [Google Scholar]
  27. Hayashi K., Hayashi M., Jalkanen M., Firestone J.H., Trelstad R.L., Bernfield M.. ( 1987;). Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study. J Histochem Cytochem 35: 1079–1088 [CrossRef] [PubMed].
    [Google Scholar]
  28. Joyce J.G., Tung J.-S., Przysiecki C.T., Cook J.C., Lehman E.D., Sands J.A., Jansen K.U., Keller P.M.. ( 1999;). The L1 major capsid protein of human papillomavirus type 11 recombinant virus-like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes. J Biol Chem 274: 5810–5822 [CrossRef] [PubMed].
    [Google Scholar]
  29. Kariya Y., Sato H., Katou N., Kariya Y., Miyazaki K.. ( 2012;). Polymerized laminin-332 matrix supports rapid and tight adhesion of keratinocytes, suppressing cell migration. PLoS One 7: e35546 [CrossRef] [PubMed].
    [Google Scholar]
  30. Kato M., Wang H., Kainulainen V., Fitzgerald M.L., Ledbetter S., Ornitz D.M., Bernfield M.. ( 1998;). Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2. Nat Med 4: 691–697 [CrossRef] [PubMed].
    [Google Scholar]
  31. Kim C.W., Goldberger O.A., Gallo R.L., Bernfield M.. ( 1994;). Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patterns. Mol Biol Cell 5: 797–805 [CrossRef] [PubMed].
    [Google Scholar]
  32. Kim H.J., Lim S.J., Kim J.Y., Kim S.Y., Kim H.J.. ( 2009;). A method for removing contaminating protein during purification of human papillomavirus type 18 L1 protein from Saccharomyces cerevisiae. Arch Pharm Res 32: 1759–1766 [CrossRef] [PubMed].
    [Google Scholar]
  33. Kines R.C., Thompson C.D., Lowy D.R., Schiller J.T., Day P.M.. ( 2009;). The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding. Proc Natl Acad Sci U S A 106: 20458–20463 [CrossRef] [PubMed].
    [Google Scholar]
  34. Knappe M., Bodevin S., Selinka H.-C., Spillmann D., Streeck R.E., Chen X.S., Lindahl U., Sapp M.. ( 2007;). Surface-exposed amino acid residues of HPV16 L1 protein mediating interaction with cell surface heparan sulfate. J Biol Chem 282: 27913–27922 [CrossRef] [PubMed].
    [Google Scholar]
  35. Koda J.E., Rapraeger A., Bernfield M.. ( 1985;). Heparan sulfate proteoglycans from mouse mammary epithelial cells. Cell surface proteoglycan as a receptor for interstitial collagens. J Biol Chem 260: 8157–8162 [PubMed].
    [Google Scholar]
  36. Lambaerts K., Wilcox-Adelman S.A., Zimmermann P.. ( 2009;). The signaling mechanisms of syndecan heparan sulfate proteoglycans. Curr Opin Cell Biol 21: 662–669 [CrossRef] [PubMed].
    [Google Scholar]
  37. Liu J., Thorp S.C.. ( 2002;). Cell surface heparan sulfate and its roles in assisting viral infections. Med Res Rev 22: 1–25 [CrossRef] [PubMed].
    [Google Scholar]
  38. Molloy S.S., Bresnahan P.A., Leppla S.H., Klimpel K.R., Thomas G.. ( 1992;). Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen. J Biol Chem 267: 16396–16402 [PubMed].
    [Google Scholar]
  39. Okamoto O., Bachy S., Odenthal U., Bernaud J., Rigal D., Lortat-Jacob H., Smyth N., Rousselle P.. ( 2003;). Normal human keratinocytes bind to the alpha3LG4/5 domain of unprocessed laminin-5 through the receptor syndecan-1. J Biol Chem 278: 44168–44177 [CrossRef] [PubMed].
    [Google Scholar]
  40. Pauza C.D., Price T.M.. ( 1988;). Human immunodeficiency virus infection of T cells and monocytes proceeds via receptor-mediated endocytosis. J Cell Biol 107: 959–968 [CrossRef] [PubMed].
    [Google Scholar]
  41. Pruessmeyer J., Martin C., Hess F.M., Schwarz N., Schmidt S., Kogel T., Hoettecke N., Schmidt B., Sechi A., other authors. ( 2010;). A disintegrin and metalloproteinase 17 (ADAM17) mediates inflammation-induced shedding of syndecan-1 and -4 by lung epithelial cells. J Biol Chem 285: 555–564 [CrossRef] [PubMed].
    [Google Scholar]
  42. Purushothaman A., Chen L., Yang Y., Sanderson R.D.. ( 2008;). Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma. J Biol Chem 283: 32628–32636 [CrossRef] [PubMed].
    [Google Scholar]
  43. Ramani V.C., Purushothaman A., Stewart M.D., Thompson C.A., Vlodavsky I., Au J.L., Sanderson R.D.. ( 2013;). The heparanase/syndecan-1 axis in cancer: mechanisms and therapies. FEBS J 280: 2294–2306 [CrossRef] [PubMed].
    [Google Scholar]
  44. Rapraeger A., Jalkanen M., Bernfield M.. ( 1986;). Cell surface proteoglycan associates with the cytoskeleton at the basolateral cell surface of mouse mammary epithelial cells. J Cell Biol 103: 2683–2696 [CrossRef] [PubMed].
    [Google Scholar]
  45. Ren X.-X., Ma L., Liu Q.-W., Li C., Huang Z., Wu L., Xiong S.-D., Wang J.-H., Wang H.-B.. ( 2014;). The molecule of DC-SIGN captures enterovirus 71 and confers dendritic cell-mediated viral trans-infection. Virol J 11: 47 [CrossRef] [PubMed].
    [Google Scholar]
  46. Richards R.M., Lowy D.R., Schiller J.T., Day P.M.. ( 2006;). Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc Natl Acad Sci U S A 103: 1522–1527 [CrossRef] [PubMed].
    [Google Scholar]
  47. Rousselle P., Beck K.. ( 2013;). Laminin 332 processing impacts cellular behavior. Cell Adhes Migr 7: 122–134 [CrossRef] [PubMed].
    [Google Scholar]
  48. Saunders S., Bernfield M.. ( 1988;). Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix. J Cell Biol 106: 423–430 [CrossRef] [PubMed].
    [Google Scholar]
  49. Schelhaas M., Shah B., Holzer M., Blattmann P., Kühling L., Day P.M., Schiller J.T., Helenius A.. ( 2012;). Entry of human papillomavirus type 16 by actin-dependent, clathrin- and lipid raft-independent endocytosis. PLoS Pathog 8: e1002657 [CrossRef] [PubMed].
    [Google Scholar]
  50. Schiller J.T., Day P.M., Kines R.C.. ( 2010;). Current understanding of the mechanism of HPV infection. Gynecol Oncol 118: S12–S17 [CrossRef] [PubMed].
    [Google Scholar]
  51. Schröter C.J., Braun M., Englert J., Beck H., Schmid H., Kalbacher H.. ( 1999;). A rapid method to separate endosomes from lysosomal contents using differential centrifugation and hypotonic lysis of lysosomes. J Immunol Methods 227: 161–168 [CrossRef] [PubMed].
    [Google Scholar]
  52. Selinka H.-C., Giroglou T., Sapp M.. ( 2002;). Analysis of the infectious entry pathway of human papillomavirus type 33 pseudovirions. Virology 299: 279–287 [CrossRef] [PubMed].
    [Google Scholar]
  53. Selinka H.-C., Florin L., Patel H.D., Freitag K., Schmidtke M., Makarov V.A., Sapp M.. ( 2007;). Inhibition of transfer to secondary receptors by heparan sulfate-binding drug or antibody induces noninfectious uptake of human papillomavirus. J Virol 81: 10970–10980 [CrossRef] [PubMed].
    [Google Scholar]
  54. Shafti-Keramat S., Handisurya A., Kriehuber E., Meneguzzi G., Slupetzky K., Kirnbauer R.. ( 2003;). Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses. J Virol 77: 13125–13135 [CrossRef] [PubMed].
    [Google Scholar]
  55. Shope R.E., Hurst E.W.. ( 1933;). Infectious papillomatosis of rabbits: with a note on the histopathology. J Exp Med 58: 607–624 [CrossRef] [PubMed].
    [Google Scholar]
  56. Smith J.L., Lidke D.S., Ozbun M.A.. ( 2008;). Virus activated filopodia promote human papillomavirus type 31 uptake from the extracellular matrix. Virology 381: 16–21 [CrossRef] [PubMed].
    [Google Scholar]
  57. Sorkin A., Duex J.E.. ( 2010;). Quantitative analysis of endocytosis and turnover of epidermal growth factor (EGF) and EGF receptor. Chapter 15, Unit 15.14 In Current Protocols in Cell Biology. Edited by Bonifacino J. S., Dasso M., Harford J. B., Lippincott-Schwartz J., Yamada K. M.. New York: Wiley;.
    [Google Scholar]
  58. Sung U., O'Rear J.J., Yurchenco P.D.. ( 1997;). Localization of heparin binding activity in recombinant laminin G domain. Eur J Biochem 250: 138–143 [CrossRef] [PubMed].
    [Google Scholar]
  59. Surviladze Z., Dziduszko A., Ozbun M.A.. ( 2012;). Essential roles for soluble virion-associated heparan sulfonated proteoglycans and growth factors in human papillomavirus infections. PLoS Pathog 8: e1002519 [CrossRef] [PubMed].
    [Google Scholar]
  60. Tokumaru S., Higashiyama S., Endo T., Nakagawa T., Miyagawa J.I., Yamamori K., Hanakawa Y., Ohmoto H., Yoshino K., other authors. ( 2000;). Ectodomain shedding of epidermal growth factor receptor ligands is required for keratinocyte migration in cutaneous wound healing. J Cell Biol 151: 209–220 [CrossRef] [PubMed].
    [Google Scholar]
  61. Yoneda A., Couchman J.R.. ( 2003;). Regulation of cytoskeletal organization by syndecan transmembrane proteoglycans. Matrix Biol 22: 25–33 [CrossRef] [PubMed].
    [Google Scholar]
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