title: Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection.
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.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gillet
authors.forename: Heiko
authors.initials: H
authors.lastname: Adler
authors.forename: Philip G
authors.initials: PG
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006023:Glycoproteins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006564:Herpesviridae / Q000276:immunology / Q000378:metabolism; D006566:Herpesviridae Infections / Q000378:metabolism*; D051379:Mice; D016366:Open Reading Frames; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D014764:Viral Proteins