Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NCI	VIROL/MICRO-20

* FARE Award Winner

Authors

• RM Schowalter
• DV Pastrana
• CB Buck

Abstract

Strong evidence suggests that Merkel cell polyomavirus (MCV) is a causative factor in the development of most highly lethal cancers arising from epidermal Merkel cells. While Merkel cell carcinoma is rare, it appears that infection with MCV is common, and many healthy people chronically shed MCV virions from the surface of their skin. In an effort to better understand the factors controlling MCV tissue tropism, we sought to characterize the cellular receptors that mediate MCV attachment to cultured cells. Although several polyomavirus species have been shown to bind cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that MCV virions instead utilized glycosaminoglycans, such as heparan sulfate (HS) and chondroitin sulfate (CS), for initial cell attachment. Using cell lines deficient in glycosaminoglycan biosynthesis, we found that specific 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 infection. 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.

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