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Title: Regulation of FMDV infection by cellular rab GTPases
Author: Johns, Helen Louise
ISNI:       0000 0001 3590 9466
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2007
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FMDV infection is initiated by virus binding to integrin receptors at the cell surface. Virus binding to the integrin triggers internalization of the virus-receptor complex which enters the cell via clathrin-dependent endocytosis. The low pH within endosomes triggers capsid disassembly and translocation of the viral RNA across the endosomal membrane into the cytosol. The precise identity of the endocytic compartment from which infection by FMDV takes place is currently unknown. Rab GTPases are central regulators of endocytosis. Each rab protein is enriched in one or more specific membrane compartments. In this study dominant-negative versions of a number of rabs are used to investigate the early events in FMDV infection of a pig kidney cell line (IBRS2). Infection is inhibited by expression of dominant-negative rab5 (which inhibits formation of early endosomes) but not by dominant-negative rab4 (which inhibits rapid recycling from early endosomes to the plasma membrane) or by dominant-negative rab9 (which inhibits trafficking from late endosomes to the Golgi). Dominant negative rab11, which inhibits a slower recycling pathway via recycling endosomes inhibits FMDV infection to an extent, although the effect of dominant-negative rab5 on infection is greater. While a dominant-negative form of rab7 (which regulates trafficking from early to late endosomes) unable to bind membranes inhibits FMDV infection, a membrane binding but inactive rab7 does not. This inhibition is shown to be at the stage of replication rather than entry. It is suggested that rab7 may be required for intracellular virus replication, possibly anchoring the replication complex to the replication vesicle.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available