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Title: The different rules of autophagy during picornavirus infections
Author: Brooks, Elizabeth
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2007
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Autophagy is widely regarded to function as a host cell defence system during intracellular infections. However, not all pathogens are degraded by autophagy. Some inhibit autophagy preventing their degradation, whilst others utilise components of the pathway for their advantage. Poliovirus is thought to require autophagy-derived membranes for replication and utilise mature autophagosomes as a pre-lytic exit strategy. Using a range of microscopy and siRNA techniques, we investigated whether the replication of two other picornaviruses, Foot-and-Mouth Disease virus (FMDV) and Bovine Enterovirus (BEV) also require autophagy-components. Here we show that FMDV infection induces the rearrangement of the autophagy marker LC3, into a unique perinuclear structure (termed FIALLS), which could be reproduced by the expression of the FMDV proteins 2BC or 2C in the absence of infection. Formation of this structure was dependant upon an intact microtubule network, and inhibition of its formation using Scriptaid, led to a decrease in virus yield by roughly one log. However, infection of autophagy-deficient cells (treated with Beclin or Atg5 siRNA), had very little effect on FMDV yield. In contrast to PV and FMDV, BEV yields actually increased (5-10 fold) in autophagy-deficient cells, suggesting it is partially degraded by autophagy. We therefore propose that FMDV and BEV do not require autophagy membranes for replication, and may be inefficiently targeted for degradation by the autophagy pathway. Furthermore, FMDV may avoid degradation by inducing the formation of FIALLS, restricting autophagy function to a small area of the cytoplasm allowing FMDV to replicate freely in autophagy-free cytoplasm.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available