Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen, Germany.
The recently discovered human Merkelcell polyomavirus (MCPyV or MCV) causes the aggressive Merkel cell carcinoma(MCC) in the skin of immunocompromised individuals. Conflicting reports suggest that cellular glycans containing sialic acid (Neu5Ac) may play a role in MCPyV infectious entry. To address this question, we solved X-ray structures of the MCPyV major capsid protein VP1 both alone and in complex with several sialylated oligosaccharides. A shallow binding site on the apical surface of the VP1 capsomer recognizes the disaccharide Neu5Ac-α2,3-Gal through a complex network of interactions. MCPyV engages Neu5Ac in an orientation and with contacts that differ markedly from those observed in other polyomavirus complexes with sialylated receptors. Mutations in the Neu5Ac binding site abolish MCPyV infection, highlighting the relevance of the Neu5Ac interaction for MCPyV entry. Our study thus provides a powerful platform for the development of MCPyV-specific vaccines and antivirals. Interestingly, engagement of sialic acid does not interfere with initial attachment of MCPyV to cells, consistent with a previous proposal that attachment is mediated by a class of non-sialylated carbohydrates called glycosaminoglycans. Our results therefore suggest a model in which sialylated glycans serve as secondary, post-attachment co-receptors during MCPyV infectious entry. Since cell-surface glycans typically serve as primary attachment receptors for many viruses, we identify here a new role for glycans in mediating, and perhaps even modulating, post-attachment entry processes.
Am old enough to understand the difference between the Bay of Pigs - and roasting a pig at a epicurian feast. Been thru the hippy, yippie and yuppie years - always remaining who I am.
Very much believe in "Sing your own song - weave your own tapestry"
Am young enough to still know the thrill of new discoveries, the beauty of the evening, to celebrate the joy of another tommorow.
Survived these many decades with a severe medical problems. Sorting out the maze of now having two lymphomas and all their nasty little companions, but I continue.
Besides, being a simple iconoclastic eclectic, have been called many things. An incurable romanticist - with a strong touch of reality. Thinker, intellectual (God, how I hate that term) - been told I am a lion with the heart of the poet.
Know how to wage war and conquer my foes - but would rather be known as one who brings hope and life. To bring hope into anothers life is the ultimate of joys.
Life should be about bringing hope, peace, vision... a sense of purpose beyond yourself.