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
2024-04-16
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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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