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dc.contributor.advisorSchwarz-Linek, Uli
dc.contributor.authorBarski, Michał S.
dc.coverage.spatialxviii, 215 p.en_US
dc.date.accessioned2016-03-11T14:55:09Z
dc.date.available2016-03-11T14:55:09Z
dc.date.issued2016-06-22
dc.identifier.urihttp://hdl.handle.net/10023/8408
dc.description.abstractBunyaviridae is one of the biggest known viral families, and includes many viruses of clinical and economic importance. The major virulence factor of most bunyaviruses is the non-structural protein (NSs). NSs is expressed early in infection and inhibits the innate immune response of the host by blocking several steps in the interferon induction and signalling pathways. Hence, NSs significantly contributes to the establishment of a successful viral infection and replication, persistent infection and the zoonotic capacity of bunyaviruses. Although functions and structures of many viral interferon antagonists are known, no structure of a bunyavirus NSs protein has been solved to date. This strongly limits our understanding of the role and the mechanism of interferon antagonism in this large virus family. In this work the first structure for a bunyavirus interferon antagonist, the core domain crystal structure of NSs from the Rift Valley fever virus (RVFV) is presented. RVFV is one of the most clinically significant members of the Bunyaviridae family, causing recurrent epidemics in Africa and Arabia, often featuring high-mortality haemorrhagic fevers. The structure shows a novel all-helical fold. The unique molecular packing of NSs in the crystal creates stable fibrillar networks, which could correspond to the characteristic fibrillation of NSs observed in vivo in the nuclei of RVFV infected cells. This first NSs structure might be a useful template for future structure-aided design of drugs that target the RVFV interferon antagonism. Attempts at characterising other bunyavirus NSs proteins of other genera were made, but were hampered by problems with obtaining sufficient amounts of soluble and folded protein. The approaches that proved unsuccessful for the solubilisation of these NSs proteins, however, should inform future experiments aimed at obtaining recombinant NSs for structural studies.en_US
dc.language.isoenen_US
dc.publisherUniversity of St Andrews
dc.subjectBunyavirusen_US
dc.subjectNSsen_US
dc.subjectNon-structural proteinen_US
dc.subjectRift Valley fever virusen_US
dc.subjectBunyaviridaeen_US
dc.subjectInterferon antagonisten_US
dc.subject.lccQR398.7B2
dc.subject.lcshBunyavirusesen_US
dc.subject.lcshViral proteinsen_US
dc.subject.lcshInterferon--Antagonistsen_US
dc.titleStructural studies of bunyavirus interferon antagonist proteinsen_US
dc.typeThesisen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.rights.embargodate2018-05-19en_US
dc.rights.embargoreasonThesis restricted in accordance with University regulations. Print and electronic copy restricted until 19th May 2018, pending formal approvalen_US


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