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  Mechanisms of persistence of canine adenoviruses


   College of Medicine and Veterinary Medicine

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  Dr A Philbey, Dr B Dalziel, Dr P Beard  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Adenoviruses produce a range of diseases in humans and animals and are used as vectors for gene therapy. 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 establish persistent infections in vitro and in naturally infected animals. There is evidence that human adenoviruses 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 and epithelial cells, will be investigated for their ability to maintain persistent CAV-1 or CAV-2 infection under a range of conditions, including exposure to interferon and inducible expression of viral regulatory genes, particularly early transcription units. Virus replication kinetics, together with gene and protein expression, will be determined. We have access to tissues from naturally infected foxes, which will be examined for evidence of CAV-1 persistence. The project will provide training in experimental techniques in cell and molecular virology. Knowledge of the ability of canine adenoviruses to establish persistent infections will contribute to our understanding of transmission of infection in natural populations of dogs and red foxes and the roles of vaccination and immunity in controlling disease. The results may also provide insights into approaches to manipulate the efficacy of adenovirus gene delivery vectors by promoting persistence in target tissues, as well as to understand how adenoviruses persist in transplanted tissues and recrudesce in immunosuppressed human patients.

Funding: This project is eligible for a University of Edinburgh 3year PhD studentship or Principal’s Career Development Studentship. ( http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/uk-eu/university-scholarships/development)

International students should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research).


Application procedures:
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be sent to: Liz Archibald, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG or emailed to [Email Address Removed].

When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.

All applicants should also apply through the University’s on-line application system for September 2017 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=826

Applicants for the Principal’s career development studentship must also complete the specific on-line application form at http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/uk-eu/university-scholarships/development

References

King, C.R., Zhang, A., Mymryk, J.S., 2016. The persistent mystery of adenovirus persistence. Trends in Microbiology 24, 323-324.

Walker, D., Fee, S.A., Hartley, G., Learmount, J., O'Hagan, M.J., Meredith, A.L., de C Bronsvoort, B.M., Porphyre, T., Sharp, C.P., Philbey, A.W., 2016. Serological and molecular epidemiology of canine adenovirus type 1 in red foxes (Vulpes vulpes) in the United Kingdom. Scientific Reports 6, 36051.

Zhang, Y., Huang, W., Ornelles, D.A., Gooding, L.R., 2010. Modeling adenovirus latency in human lymphocyte cell lines. Journal of Virology 84, 8799-8810.

Where will I study?

 About the Project