Mechanisms of persistence of canine adenoviruses

Adenoviruses produce a range of diseases in humans and animals and are used as gene therapy vectors. Reactivation of adenoviruses can be a problem in human transplant recipients. Canine adenovirus type 1 (CAV-1) causes infectious canine hepatitis in dogs and foxes, whilst canine adenovirus type 2 (CAV-2) causes upper respiratory disease in dogs. Our group has shown that red foxes are a wildlife reservoir of CAV-1 and that the virus appears to establish persistent infections in healthy animals. This project will use cell culture and molecular virology techniques to explore the mechanisms by which canine adenoviruses are able to establish persistent infections in vitro and in naturally infected animals. There is evidence that human adenoviruses are able to establish persistent infections in lymphocytes and that latency in these cells is controlled by interferon. We have an established system for growing CAV-1 and CAV-2 in Madin-Darby canine kidney (MDCK) cells. MDCK and other canine cell lines, along with primary lymphoid, epithelial and mesenchymal cells, will be investigated for their ability to maintain persistent CAV-1 or CAV-2 infections under a range of experimental conditions, including exposure to serum, interferon and inducible expression of viral regulatory genes. Virus replication kinetics, along with gene and protein expression, in cell culture will be determined. We also have access to tissues from naturally infected foxes, which will be examined for further evidence of CAV-1 persistence. The project will provide training in cell culture and molecular virology techniques. Knowledge of the ability of canine adenoviruses to establish persistent infections will help us to understand transmission of infection in natural populations of dogs and foxes, and the role of vaccination and immunity in controlling disease. The results may provide insights into approaches to manipulate the efficacy of adenovirus gene delivery vectors by promoting their persistence in target tissues.

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ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 16th January 2018