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Title: Regulation of FMDV infection by cellular rab GTPases
Author: Johns, Helen Louise
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 ofthe virus-receptor complex which enters the cell via clathrin-dependent endocytosis. The low pH within endosomes triggers capsid disassembly and translocation ofthe viral RNA across the endosomal membrane into the cytosol. The precise identity ofthe endocytic compartment from which infection by FMDV takes place is currently unknown. Rab GTPases are central regulators ofendocytosis. Each rab protein is enriched in one or more specific membrane compartments. In this study dominant-negative versions ofa number ofrabs are used to investigate the early events in FMDV infection ofa pig kidney cell line (IBRS2). Infection is inhibited by expression of dominant-negative rab5 (which inhibits formation ofearly cndosomes) but not by dominant-negative raM (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 ofdominant-negative rab5 on infection is greater. While a dominant-negative form ofrab7 (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: University of Surrey, 2007 Qualification Level: Doctoral
EThOS ID:  DOI: Not available