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Crystallographic studies of the Crimean-Congo haemorrhagic fever virus and tomato spotted wilt virus N proteins

Carter, Stephen D. (2015) Crystallographic studies of the Crimean-Congo haemorrhagic fever virus and tomato spotted wilt virus N proteins. PhD thesis, University of Leeds.

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Abstract

The Bunyaviridae family is a group of segmented negative sense RNA viruses (sNSV) that cause severe disease in both plants and humans. This group of viruses is further classified into the Orthobunyavirus, Tospovirus, Nairovirus, Phlebovirus and Hantavirus genera. Crimean-Congo haemorrhagic fever (CCHF) is a potentially fatal tick borne viral meta-zoonotic haemorrhagic disease, which is caused by Crimean-Congo haemorrhagic fever virus (CCHFV), a member of the Nairovirus genus. Despite the medical importance and severity of disease, the molecular biology of CCHFV remains poorly understood, primarily because outbreaks are sporadic, and its handling requires the highest containment facilities, bio-safety level 4 (BSL-4). Tomato spotted wilt virus (TSWV) is a member of the Tospovirus genus, which are the only plant infecting members of the bunyaviruses. TSWV causes serious disease in over 80 plant families, including peppers, potatoes, lettuce and tomatos, causing approximately 80 million dollars worth of loss to the food industry per year. The pathogenesis of CCHFV and TSWV depends on the formation of the ribonucleoprotein (RNP) complex, in which their genomes and antigenome are entirely encapsidated by the virus-encoded nucleocapsid (N) protein. Only in the form of the RNP is the genome replicated, transcribed and packaged into new progeny particles. This work has implemented X-ray crystallography to better understand the structural and functional roles of the CCHFV and TSWV N proteins. This work presents the 2.1 Å crystal structure of the CCHFV N protein, which shows a high degree of structural homology with the N protein from another sNSV member Lassa virus (LASV), and reveals important insight into sNSV phylogenetics, and the interaction of CCHFV with the host cell. This work also includes the expression, purification, and crystallization of the TSWV N protein. Crystals generated from TSWV N protein diffracted to 2.6 Å and structure determination is ongoing.

Item Type: Thesis (PhD)
Keywords: Nucleocapsid, Virus, X-ray crystallography
Academic Units: The University of Leeds > University of Leeds Research Centres and Institutes > Astbury Centre for Structural Molecular Biology (Leeds)
The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute for Molecular and Cellular Biology (Leeds)
Identification Number/EthosID: uk.bl.ethos.640645
Depositing User: Mr Stephen D. Carter
Date Deposited: 17 Mar 2015 15:15
Last Modified: 25 Nov 2015 13:48
URI: http://etheses.whiterose.ac.uk/id/eprint/8304

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