Autophagy represents a new host-pathogen interface for identification of infectious bronchitis virus proteins that determine virulence

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The overall aim of the project is to study the role of the IBV replicase proteins in the modulation of autophagy; such proteins are highly likely to represent new determinants of virulence, and possibly host range. The objectives are: 1) - to generate a library of chimaeric viruses where defined replicase genes have been exchanged between virulent and avirulent IBV strains. These will be used to see if virulence segregates with individual or specific combinations of replicase proteins.; 2) and 3) - to determine if autophagy is activated during IBV infection, and determine whether autophagy enhances or suppresses IBV replication and virulence. If autophagy enhances IBV replication and virulence, for example by providing membranes necessary for replication, we argue that virulence will be determined by replicase proteins that stimulate autophagy. Conversely, suppression of replication by autophagy would point to replicase proteins that suppress autophagosome production and inhibit the cellular defence provided by autophagy. 4) and 5) - to address this issue by determining whether the IBV replicase physically associates with autophagosomes, and by identifying IBV replicase proteins that can either alone, or in combination, modulate autophagy and autophagosome production; 6) - using the library of IBV chimeras where replicase genes have been exchanged between virulent and avirulent IBV we anticipate that virulence will segregate with individual or specific combinations, of replicase proteins. The link with autophagy will be made if we can establish that virulence correlates with sensitivity of viruses to autophagy, and demonstrate that replicase proteins that are able to confer virulence are able to modulate autophagy.

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