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Updated: Jul 15, 2026

Measurement of γHV68 Infection in Mice
Published on: November 22, 2011
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.
Abstract:
Glycosaminoglycans (GAGs) commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68) infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces.
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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