1887

Abstract

Many herpesviruses bind to heparan sulfate (HS). Murid herpesvirus-4 (MuHV-4) does so via its envelope glycoproteins gp70 and gH/gL. MuHV-4 gp150 further regulates an HS-independent interaction to make that HS-dependent too. Cell binding by MuHV-4 virions is consequently strongly HS-dependent. Gp70 and gH/gL show some redundancy: an antibody-mediated blockade of HS binding by one is well tolerated, whereas a blockade of both severely impairs infection. In order to understand the importance of HS binding for MuHV-4 , we generated mutants lacking both gL and gp70. As expected, gLgp70 MuHV-4 showed very poor cell binding. It infected mice at high dose but not at low dose, indicating defective host entry. But once entry occurred, host colonization, which for MuHV-4 is relatively independent of the infection dose, was remarkably normal. The gLgp70 entry deficit was much greater than that of gL or gp70 single knockouts. And gp150 disruption, which allows HS-independent cell binding, largely rescued the gLgp70 cell binding and host entry deficits. Thus, it appeared that MuHV-4 HS binding is important , principally for efficient host entry.

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2009-03-01
2019-11-14
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References

  1. Adler, H., Messerle, M., Wagner, M. & Koszinowski, U. H. ( 2000; ). Cloning and mutagenesis of the murine gammaherpesvirus 68 genome as an infectious bacterial artificial chromosome. J Virol 74, 6964–6974.[CrossRef]
    [Google Scholar]
  2. Akula, S. M., Pramod, N. P., Wang, F. Z. & Chandran, B. ( 2001; ). Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties. Virology 284, 235–249.[CrossRef]
    [Google Scholar]
  3. Bennett, N. J., May, J. S. & Stevenson, P. G. ( 2005; ). Gamma-herpesvirus latency requires T cell evasion during episome maintenance. PLoS Biol 3, e120 [CrossRef]
    [Google Scholar]
  4. Bernfield, M., Gotte, 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]
    [Google Scholar]
  5. Birkmann, A., Mahr, K., Ensser, A., Yaguboglu, S., Titgemeyer, F., Fleckenstein, B. & Neipel, F. ( 2001; ). Cell surface heparan sulfate is a receptor for human herpesvirus 8 and interacts with envelope glycoprotein K8.1. J Virol 75, 11583–11593.[CrossRef]
    [Google Scholar]
  6. Coleman, H. M., de Lima, B., Morton, V. & Stevenson, P. G. ( 2003; ). Murine gammaherpesvirus 68 lacking thymidine kinase shows severe attenuation of lytic cycle replication in vivo but still establishes latency. J Virol 77, 2410–2417.[CrossRef]
    [Google Scholar]
  7. de Lima, B. D., May, J. S. & Stevenson, P. G. ( 2004; ). Murine gammaherpesvirus 68 lacking gp150 shows defective virion release but establishes normal latency in vivo. J Virol 78, 5103–5112.[CrossRef]
    [Google Scholar]
  8. Efstathiou, S., Ho, Y. M. & Minson, A. C. ( 1990; ). Cloning and molecular characterization of the murine herpesvirus 68 genome. J Gen Virol 71, 1355–1364.[CrossRef]
    [Google Scholar]
  9. Esclatine, A., Bellon, A., Michelson, S., Servin, A. L., Quéro, A. M. & Géniteau-Legendre, M. ( 2001; ). Differentiation-dependent redistribution of heparan sulfate in epithelial intestinal Caco-2 cells leads to basolateral entry of cytomegalovirus. Virology 289, 23–33.[CrossRef]
    [Google Scholar]
  10. Gill, M. B., Gillet, L., Colaco, S., May, J. S., de Lima, B. D. & Stevenson, P. G. ( 2006; ). Murine gammaherpesvirus-68 glycoprotein H-glycoprotein L complex is a major target for neutralizing monoclonal antibodies. J Gen Virol 87, 1465–1475.[CrossRef]
    [Google Scholar]
  11. Gillet, L. & Stevenson, P. G. ( 2007a; ). Antibody evasion by the N terminus of murid herpesvirus-4 glycoprotein B. EMBO J 26, 5131–5142.[CrossRef]
    [Google Scholar]
  12. Gillet, L. & Stevenson, P. G. ( 2007b; ). Evidence for a multiprotein gamma-2 herpesvirus entry complex. J Virol 81, 13082–13091.[CrossRef]
    [Google Scholar]
  13. Gillet, L., Gill, M. B., Colaco, S., Smith, C. M. & Stevenson, P. G. ( 2006; ). The murine gammaherpesvirus-68 glycoprotein B presents a difficult neutralization target to monoclonal antibodies derived from infected mice. J Gen Virol 87, 3515–3527.[CrossRef]
    [Google Scholar]
  14. Gillet, L., Adler, H. & Stevenson, P. G. ( 2007a; ). Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. PLoS One 2, e347 [CrossRef]
    [Google Scholar]
  15. Gillet, L., May, J. S., Colaco, S. & Stevenson, P. G. ( 2007b; ). Glycoprotein L disruption reveals two functional forms of the murine gammaherpesvirus-68 glycoprotein H. J Virol 81, 280–291.[CrossRef]
    [Google Scholar]
  16. Gillet, L., May, J. S. & Stevenson, P. G. ( 2007c; ). Post-exposure vaccination improves gammaherpesvirus neutralization. PLoS One 2, e899 [CrossRef]
    [Google Scholar]
  17. Gillet, L., May, J. S., Colaco, S. & Stevenson, P. G. ( 2007d; ). The murine gammaherpesvirus-68 gp150 acts as an immunogenic decoy to limit virion neutralization. PLoS One 2, e705 [CrossRef]
    [Google Scholar]
  18. Gillet, L., Colaco, S. & Stevenson, P. G. ( 2008a; ). The murid herpesvirus-4 gH/gL binds to glycosaminoglycans. PLoS One 3, e1669 [CrossRef]
    [Google Scholar]
  19. Gillet, L., Colaco, S. & Stevenson, P. G. ( 2008b; ). The murid herpesvirus-4 gL regulates an entry-associated conformation change in gH. PLoS One 3, e2811 [CrossRef]
    [Google Scholar]
  20. 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]
    [Google Scholar]
  21. Herold, B. C., Visalli, R. J., Susmarski, N., Brandt, C. R. & Spear, P. G. ( 1994; ). Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B. J Gen Virol 75, 1211–1222.[CrossRef]
    [Google Scholar]
  22. Kapadia, S. B., Molina, H., van Berkel, V., Speck, S. H. & Virgin, H. W. ( 1999; ). Murine gammaherpesvirus 68 encodes a functional regulator of complement activation. J Virol 73, 7658–7670.
    [Google Scholar]
  23. Kapadia, S. B., Levine, B., Speck, S. H. & Virgin, H. W. ( 2002; ). Critical role of complement and viral evasion of complement in acute, persistent and latent γ-herpesvirus infection. Immunity 17, 143–155.[CrossRef]
    [Google Scholar]
  24. Kayhan, B., Yager, E. J., Lanzer, K., Cookenham, T., Jia, Q., Wu, T. T., Woodland, D. L., Sun, R. & Blackman, M. A. ( 2007; ). A replication-deficient murine gamma-herpesvirus blocked in late viral gene expression can establish latency and elicit protective cellular immunity. J Immunol 179, 8392–8402.[CrossRef]
    [Google Scholar]
  25. Laquerre, S., Argnani, R., Anderson, D. B., Zucchini, S., Manservigi, R. & Glorioso, J. C. ( 1998; ). Heparan sulfate proteoglycan binding by herpes simplex virus type 1 glycoproteins B and C, which differ in their contributions to virus attachment, penetration, and cell-to-cell spread. J Virol 72, 6119–6130.
    [Google Scholar]
  26. Mark, L., Lee, W. H., Spiller, O. B., Villoutreix, B. O. & Blom, A. M. ( 2006; ). The Kaposi's sarcoma-associated herpesvirus complement control protein (KCP) binds to heparin and cell surfaces via positively charged amino acids in CCP1–2. Mol Immunol 43, 1665–1675.[CrossRef]
    [Google Scholar]
  27. May, J. S., Coleman, H. M., Smillie, B., Efstathiou, S. & Stevenson, P. G. ( 2004; ). Forced lytic replication impairs host colonization by a latency-deficient mutant of murine gammaherpesvirus-68. J Gen Virol 85, 137–146.[CrossRef]
    [Google Scholar]
  28. May, J. S., Coleman, H. M., Boname, J. M. & Stevenson, P. G. ( 2005a; ). Murine gammaherpesvirus-68 ORF28 encodes a non-essential virion glycoprotein. J Gen Virol 86, 919–928.[CrossRef]
    [Google Scholar]
  29. May, J. S., Colaco, S. & Stevenson, P. G. ( 2005b; ). Glycoprotein M is an essential lytic replication protein of the murine gammaherpesvirus 68. J Virol 79, 3459–3467.[CrossRef]
    [Google Scholar]
  30. May, J. S., de Lima, B. D., Colaco, S. & Stevenson, P. G. ( 2005c; ). Intercellular gamma-herpesvirus dissemination involves co-ordinated intracellular membrane protein transport. Traffic 6, 780–793.[CrossRef]
    [Google Scholar]
  31. Morin, M. J., Warner, A. & Fields, B. N. ( 1994; ). A pathway for entry of reoviruses into the host through M cells of the respiratory tract. J Exp Med 180, 1523–1527.[CrossRef]
    [Google Scholar]
  32. Moser, J. M., Farrell, M. L., Krug, L. T., Upton, J. W. & Speck, S. H. ( 2006; ). A gammaherpesvirus 68 gene 50 null mutant establishes long-term latency in the lung but fails to vaccinate against a wild-type virus challenge. J Virol 80, 1592–1598.[CrossRef]
    [Google Scholar]
  33. 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]
    [Google Scholar]
  34. Rux, A. H., Lou, H., Lambris, J. D., Friedman, H. M., Eisenberg, R. J. & Cohen, G. H. ( 2002; ). Kinetic analysis of glycoprotein C of herpes simplex virus types 1 and 2 binding to heparin, heparan sulfate and complement component C3b. Virology 294, 324–332.[CrossRef]
    [Google Scholar]
  35. Shannon-Lowe, C. D., Neuhierl, B., Baldwin, G., Rickinson, A. B. & Delecluse, H. J. ( 2006; ). Resting B cells as a transfer vehicle for Epstein–Barr virus infection of epithelial cells. Proc Natl Acad Sci U S A 103, 7065–7070.[CrossRef]
    [Google Scholar]
  36. Shukla, D. & Spear, P. G. ( 2001; ). Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. J Clin Invest 108, 503–510.[CrossRef]
    [Google Scholar]
  37. Smith, C. M., Gill, M. B., May, J. S. & Stevenson, P. G. ( 2007; ). Murine gammaherpesvirus-68 inhibits antigen presentation by dendritic cells. PLoS One 2, e1048 [CrossRef]
    [Google Scholar]
  38. Spillmann, D. ( 2001; ). Heparan sulfate: anchor for viral intruders? Biochimie 83, 811–817.[CrossRef]
    [Google Scholar]
  39. Stevenson, P. G., Belz, G. T., Castrucci, M. R., Altman, J. D. & Doherty, P. C. ( 1999; ). A γ-herpesvirus sneaks through a CD8+ T cell response primed to a lytic-phase epitope. Proc Natl Acad Sci U S A 96, 9281–9286.[CrossRef]
    [Google Scholar]
  40. Stevenson, P. G., May, J. S., Smith, X. G., Marques, S., Adler, H., Koszinowski, U. H., Simas, J. P. & Efstathiou, S. ( 2002; ). K3-mediated evasion of CD8+ T cells aids amplification of a latent γ-herpesvirus. Nat Immunol 3, 733–740.
    [Google Scholar]
  41. Wang, F. Z., Akula, S. M., Pramod, N. P., Zeng, L. & Chandran, B. ( 2001; ). Human herpesvirus 8 envelope glycoprotein K8.1A interaction with the target cells involves heparan sulfate. J Virol 75, 7517–7527.[CrossRef]
    [Google Scholar]
  42. Wolf, J. L., Rubin, D. H., Finberg, R., Kauffman, R. S., Sharpe, A. H., Trier, J. S. & Fields, B. N. ( 1981; ). Intestinal M cells: a pathway for entry of reovirus into the host. Science 212, 471–472.[CrossRef]
    [Google Scholar]
  43. Yamashita, Y., Oritani, K., Miyoshi, E. K., Wall, R., Bernfield, M. & Kincade, P. W. ( 1999; ). Syndecan-4 is expressed by B lineage lymphocytes and can transmit a signal for formation of dendritic processes. J Immunol 162, 5940–5948.
    [Google Scholar]
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