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Title: The effects of foot and mouth disease virus 2BC protein upon the secretory pathway
Author: Fullen, Daniel Joseph
ISNI:       0000 0004 2716 1613
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2011
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The secretory pathway of cells is important for the trafficking of proteins to the cell surface. Virus-mediated perturbations in the secretory pathway can result in inhibition of expression of MHC I molecules on the cell surface, and/or inhibition of the secretion of cytokines, which may contribute to virus evasion of the immune response. Previous studies have shown that the 3A protein of polio- and coxsackieviruses, and the 2BC protein of foot-and-mouth disease virus (FMDV) block protein trafficking. Using cells transfected with a plasmid expressing 2BC and fluorescent microscopy, Western blotting and a range of protein expression systems, the effects of the FMDV 2BC protein on the secretory pathway were investigated further. These studies confirmed that FMDV 2BC inhibits protein trafficking and demonstrated that 2BC co-localises with the ER protein calnexin and appeared to deplete the expression of the COP II marker Sec31A, the ERGIC marker ERGIC-53 and the COP I marker B-Cop. Furthermore, FMDV 2BC and 2C expression inhibited the expression of secreted alkaline phosphatase (SEAP), used to monitor the secretory pathway. The effect of 2BC on SEAP expression was not mediated at the transcriptional level. FMDV 2BC also suppressed the expression of a non-secretory reporter protein, β-galactosidase. In order to determine if these effects were mediated by ER stress and the unfolded protein response, the effect of FMDV infection on expression of ER stress proteins in cells was investigated. These preliminary studies suggested that FMDV infection stimulates or alters the expression of ER stress markers.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available