Aug 11, 2011

Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry

PLoS Pathogens
Rachel SchowalterChristopher B Buck

Abstract

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 resi...Continue Reading

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  • Citations64

Citations

Mentioned in this Paper

Malignant Neoplasm of Skin
Real-Time Polymerase Chain Reaction
Cricetulus
Flow Cytometry
Chinese Hamster
Biochemical Pathway
Chondroitin Sulfate, Zinc Salt
Melanocyte
Amidophosphoribosyltransferase
Chondroitin

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