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Title: Arenaviral nucleoproteins and the identification of their cellular interacting partners
Author: Buckley, Andrew Dennis
ISNI:       0000 0004 5918 2136
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2016
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Members of the Arenaviridae family are able to cause severe disease in humans. The members of this family which induce haemorrhagic fever (HF) are responsible for over 300,000 reported cases per annum, making arenaviruses the largest cause of HF worldwide. Complications from arenavirus induced disease vary from cerebral and developmental complications in infants and the immunocompromised, to HF with cases ultimately fatal in up to 80% of cases. HF causing arenaviruses can induce high grade fever; diarrhoea; vomiting and general malaise, leading to loss of vascular permeability; internal haemorrhaging; disseminated intravascular coagulation and coma. Fundamental mechanisms of the viral replication strategies are currently unknown, it is therefore of paramount importance to increase knowledge in this area in order to identify potential therapeutic strategies. The nucleoprotein (NP) of arenaviruses is essential for viral replication, and is thus a good candidate for further investigation. This study presents the analysis of the host-cell interactome of the HF causing Lujo virus (LUJV) NP, an arenaviral infection associated with 80% mortality. The NP of LUJV was found to associate with members of the translation initiation and elongation complexes by immunoprecipitation and immunofluorescence microscopy. In addition, the NP of the congenital pathogen lymphocytic choriomeningitis virus was found to co-localise with translation associated proteins, with such proteins also identified within viral particles. Finally, it is demonstrated here that the translation of arenaviral-like mRNAs is enhanced in the presence of NP, through a mechanism predicted to be driven by the association of NP with the translation initiation complex eIF4F and the circularisation of mRNAs.
Supervisor: Barr, John N. ; Hewson, Roger Sponsor: Public Health England
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available