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Title: Early events in cell entry by foot-and-mouth disease virus
Author: Berryman, Stephen John
ISNI:       0000 0001 3462 0636
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2005
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The studies presented in this thesis demonstrate that foot-and-mouth disease virus (FMDV) infection mediated by the integrin ?v?6 takes place through clathrin-dependent endocytosis. Inhibition of clathrin-dependent endocytosis by sucrose treatment or transient expression of a dominant-negative version of AP180 inhibited virus entry and infection. Similarly, inhibition of endosomal acidification inhibited an early step in infection. Blocking endosomal acidification did not interfere with surface expression of alphavbeta6, virus binding to the cells, uptake of the virus into endosomes, or cytoplasmic virus replication. These observations suggest that the low pH within endosomes is required for a post-entry step of infection, most likely capsid uncoating and delivery of viral RNA into the cytosol. FMDV infection occurred in the absence of caveolae and inhibition of lipid-raft dependent endocytosis did not inhibit virus uptake or infection. Using immunofluorescence confocal microscopy, FMDV colocalised with alphavbeta6 at the cell surface but not with the B subunit of cholera toxin, a marker for lipid rafts. At 37°C, virus was rapidly taken up into the cells and colocalised with markers for early and recycling endosomes but not with a marker for lysosomes, suggesting that infection occurs from within the early or recycling endosomal compartments. This conclusion was supported by the observation that FMDV infection is not inhibited by nocodazole, a reagent that inhibits vesicular trafficking between early and late endosomes (and hence trafficking to lysosomes). Internalisation of alphavbeta6 and its accumulation in early and recycling endosomes was triggered by virus binding, suggesting that the integrin serves not only as an attachment receptor but also to deliver the virus to the acidic endosomes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available