Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection.
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...
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Public Library of Science (PLoS)
2007-04-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000347&type=printable |
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| author | Laurent Gillet Heiko Adler Philip G Stevenson |
| author_facet | Laurent Gillet Heiko Adler Philip G Stevenson |
| author_sort | Laurent Gillet |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-25e60c3701034c5686d2137caf3d8e3a |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2007-04-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-25e60c3701034c5686d2137caf3d8e3a2025-08-20T02:38:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-04-0124e34710.1371/journal.pone.0000347Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection.Laurent GilletHeiko AdlerPhilip G StevensonGlycosaminoglycans (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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000347&type=printable |
| spellingShingle | Laurent Gillet Heiko Adler Philip G Stevenson Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. PLoS ONE |
| title | Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. |
| title_full | Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. |
| title_fullStr | Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. |
| title_full_unstemmed | Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. |
| title_short | Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. |
| title_sort | glycosaminoglycan interactions in murine gammaherpesvirus 68 infection |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000347&type=printable |
| work_keys_str_mv | AT laurentgillet glycosaminoglycaninteractionsinmurinegammaherpesvirus68infection AT heikoadler glycosaminoglycaninteractionsinmurinegammaherpesvirus68infection AT philipgstevenson glycosaminoglycaninteractionsinmurinegammaherpesvirus68infection |