Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.

Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the...

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Autores principales:	Rachel M Schowalter, Diana V Pastrana, Christopher B Buck
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e181bee748d043e6863a0cd4e74e0a61
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spelling	oai:doaj.org-article:e181bee748d043e6863a0cd4e74e0a612021-11-18T06:03:09ZGlycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.1553-73661553-737410.1371/journal.ppat.1002161https://doaj.org/article/e181bee748d043e6863a0cd4e74e0a612011-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829355/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus.Rachel M SchowalterDiana V PastranaChristopher B BuckPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 7, p e1002161 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Rachel M Schowalter Diana V Pastrana Christopher B Buck Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.
description	Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus.
format	article
author	Rachel M Schowalter Diana V Pastrana Christopher B Buck
author_facet	Rachel M Schowalter Diana V Pastrana Christopher B Buck
author_sort	Rachel M Schowalter
title	Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.
title_short	Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.
title_full	Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.
title_fullStr	Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.
title_full_unstemmed	Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.
title_sort	glycosaminoglycans and sialylated glycans sequentially facilitate merkel cell polyomavirus infectious entry.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/e181bee748d043e6863a0cd4e74e0a61
work_keys_str_mv	AT rachelmschowalter glycosaminoglycansandsialylatedglycanssequentiallyfacilitatemerkelcellpolyomavirusinfectiousentry AT dianavpastrana glycosaminoglycansandsialylatedglycanssequentiallyfacilitatemerkelcellpolyomavirusinfectiousentry AT christopherbbuck glycosaminoglycansandsialylatedglycanssequentiallyfacilitatemerkelcellpolyomavirusinfectiousentry
_version_	1718424700005122048

Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.

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