Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection

Laurent Gillet1, Heiko Adler, Philip G Stevenson

  • 1Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

Plos One
|April 5, 2007
PubMed

Insights

Murine gamma-herpesvirus-68 (MHV-68) uses gp70, not gp150, for glycosaminoglycan (GAG) binding. ORF4 protein likely prevents premature GAG interaction, facilitating cell entry.

Area of Science:

  • Virology
  • Glycobiology
  • Cellular Biology

Background:

  • Glycosaminoglycans (GAGs) are crucial for herpesvirus entry, mediating initial cell attachment.
  • Murine gamma-herpesvirus-68 (MHV-68) infection heavily relies on GAGs, with gp150 previously thought to be the primary viral GAG-binding protein.

Purpose of the Study:

  • To identify the major glycosaminoglycan (GAG)-binding protein of Murine gamma-herpesvirus-68 (MHV-68).
  • To elucidate the role of viral GAG-binding proteins in MHV-68 cell entry and infection dynamics.

Main Methods:

  • Analysis of GAG-binding properties of MHV-68 viral proteins, including gp70 and gp150.
  • Generation and characterization of ORF4-deficient MHV-68 mutants.
  • Assessment of viral binding to cells and inhibition by soluble heparin.

Main Results:

  • The primary GAG-binding protein of MHV-68 was identified as gp70, a product of ORF4, not gp150.
  • ORF4-deficient MHV-68 exhibited normal cell binding but increased sensitivity to soluble heparin inhibition.
  • A significant portion of gp70's GAG-binding domain is cleaved post-translationally, suggesting a regulatory role for ORF4.

Conclusions:

  • Viral protein gp70, not gp150, is the major GAG-binding protein in MHV-68.
  • The ORF4 protein likely functions to sequester soluble GAGs, preventing premature interaction with gp150 and modulating viral entry.
  • gp150 may act as a GAG-sensitive switch, regulating MHV-68 cell surface entry.

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