<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Deciphering structural variations within the norovirus capsid"^^ . "Norovirus is one of the most common agents associated with acute gastroenteritis. Despite its\r\ndiscovery 50 years ago, as of now there is no cure or treatment, and knowledge about the\r\ninfection cycle of norovirus is still limited.\r\nUsing cryo-electron microscopy, we determined the structure of different clinically relevant\r\nGII.4 strain virus like particles (VLPs), and an engineered version of GII.4 that is in use as\r\nvaccine candidate. Unexpectedly we found that these empty particles were composed of 240\r\ncopies of VP1 instead of the typical 180. We could show that this conformation is only\r\nadopted by GII.4 strain VLPs, and that norovirus virions most likely assemble into T=3\r\nicosahedral particles. Conversely, VP1 of GII.17, another strain that has become clinically\r\nrelevant in the last years, assembled into the characteristic T=3 icosahedral capsid, as\r\ndetermined by cryo-electron microscopy.\r\nMoreover, we characterized a panel of GII.4 specific Nanobodies and determined their\r\nbinding sites and influence on particle integrity using cryo-electron microscopy. Several\r\nNanobodies had a strong inhibition potential in surrogate assays against GII.4 VLPs, but\r\ncross-reactivity to other strains was low. Structures of Nanobody/VLP complexes revealed\r\nthat the Nanobodies bound to a similar site on the lower part of the P domain. Moreover, the\r\nstructures showed that the P domains were flexibly rotated to distinct positions, but generally\r\nparticle conformation remained intact.\r\nLikewise, we also worked on three GI.1 specific Nanobodies and found two Nanobodies with\r\ngreat inhibition potential. Importantly, we found that combination of Nanobody with the\r\nhuman milk oligosaccharide 2’FL was able to synergistically improve attachment inhibition\r\nof VLPs to histo-blood group antigens, suggesting the use of combinational treatment against\r\nnorovirus infection.\r\nIn another study, we found that murine norovirus, which is commonly used as a model system\r\nfor human norovirus, is undergoing severe structural rearrangements after incubation with\r\nions, such as MgCl2 and CaCl2. The normally extended P domains are collapsing onto the\r\nshell, accompanied by a rotational movement. Most likely, this movement is important to\r\nfacilitate infection. Importantly, we also characterized a Nanobody that was binding to the\r\nlower part of the P domain, effectively inhibiting MNV infection by blocking this movement.\r\nTaken together, these results broaden the understanding on general norovirus structure and\r\nhow noroviruses are interacting with antivirals and cofactors. Our basic research broadens the understanding of norovirus internal differences and capsid flexibilities, and can ultimately aid\r\nin the development of a more effective treatment for norovirus infections."^^ . "2020" . . . . . . . "Jessica Michelle"^^ . "Devant"^^ . "Jessica Michelle Devant"^^ . . . . . . "Deciphering structural variations within the norovirus capsid (PDF)"^^ . . . "Deciphering structural variations within the norovirus capsid_final_pdf_A.pdf"^^ . . . "Deciphering structural variations within the norovirus capsid (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Deciphering structural variations within the norovirus capsid (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Deciphering structural variations within the norovirus capsid (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Deciphering structural variations within the norovirus capsid (Other)"^^ . . . . . . "small.jpg"^^ . . . "Deciphering structural variations within the norovirus capsid (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #28634 \n\nDeciphering structural variations within the norovirus capsid\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .