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Title: Investigation into infectious bronchitis virus (IBV) spike glycoprotein glycosylation, pathogenicity and tropism
Author: Stevenson-Leggett, P.
ISNI:       0000 0004 7964 1467
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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Infectious bronchitis virus (IBV) is the most economically damaging virus to the poultry industry, presenting a major threat to the health and productivity of both commercial and backyard flocks. Better understanding of the molecular mechanisms involved in virus infection and the properties that allow it to be such a successful pathogen is required to improve vaccination strategies and control of the disease. The spike (S) protein of IBV is responsible for attachment and entry into host cells. Like other viral attachment proteins, IBV S is highly glycosylated. Using mass spectrometry techniques as well as cellular inhibitors and deglycosylating enzymes, the glycan profile of IBV was further elucidated and a possible role for glycosylation in reducing antibody binding was suggested. The role of the S protein in pathogenicity is somewhat unclear. Previous studies have investigated IBV pathogenicity using recombinant viruses with a non-pathogenic backbone expressing heterologous spikes. In the present study, the S gene has been modified within a pathogenic backbone to assess the potential to alter pathogenicity. Firstly, a pathogenic virus expressing a non-pathogenic S protein was generated and characterised in vitro and in vivo. These studies revealed that the S gene was a factor in IBV pathogenicity. This was confirmed as a gene-specific effect through the generation and characterisation of a second virus, expressing the S protein from a heterologous pathogenic strain of IBV. This virus retained the ability to cause disease despite replacement of the S gene. Defining the cellular factors required by the virus to enter and successfully replicate in a given cell enables propagation of viruses not usually able to replicate in cell culture. Lastly, the cellular conditions necessary for IBV infection were investigated in the context of protease cleavage of the spike glycoprotein and in terms of temperature sensitivity, offering a possible mechanism of attenuation in some strains and a platform for more efficient vaccine production.
Supervisor: Hiscox, Julian ; Bickerton, Erica ; Iqbal, Munir Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral