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CryoEM Structure of Merkel Cell Polyomavirus Virus-like Particle
Structural highlights
Publication Abstract from PubMedMerkel cell polyomavirus (MCPyV) is a human double-stranded DNA tumor virus. MCPyV cell entry is unique among the polyomavirus family as it requires the engagement of two types of glycans, sialylated oligosaccharides and sulfated glycosaminoglycans (GAGs). Here, we present crystallographic and cryo-electron microscopic structures of the icosahedral MCPyV capsid and analysis of its glycan interactions via NMR spectroscopy. While sialic acid binding is specific for alpha2-3-linked sialic acid and mediated by the exposed apical loops of the major capsid protein VP1, a broad range of GAG oligosaccharides bind to recessed regions between VP1 capsomers. Individual VP1 capsomers are tethered to one another by an extensive disulfide network that differs in architecture from previously-described interactions for other PyVs. An unusual C-terminal extension in MCPyV VP1 projects from the recessed capsid regions. Mutagenesis experiments show that this extension is dispensable for receptor interaction.IMPORTANCEThe MCPyV genome was found to be clonally integrated in 80% of Merkel cell carcinoma (MCC), a rare but aggressive form of human skin cancer, strongly suggesting that this virus is tumorigenic. In the metastasizing state the course of disease is often fatal, especially in immunocompromised individuals, as reflected by the high mortality rate of 33-46% and low 5-year survival rate (< 45%). The high seroprevalence of about 60% makes MCPyV a serious healthcare burden and illustrates the need for targeted treatments. In this study we present the first high-resolution structural data of this human tumor virus and demonstrate that the full capsid is required for the essential interaction with its GAG receptor(s). Together this data can be used as a basis for future strategies in drug development. Structure of Merkel cell polyomavirus capsid and interaction with its glycosaminoglycan attachment receptor.,Bayer NJ, Januliene D, Zocher G, Stehle T, Moeller A, Blaum BS J Virol. 2020 Jul 22. pii: JVI.01664-19. doi: 10.1128/JVI.01664-19. PMID:32699083[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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