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  “Not all viruses come alone” - the impact of orbivirus co-infections on bluetongue virus reassortment and diversity


   Pirbright Laboratory, Surrey, Outer London

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  Dr Karin Darpel, Prof Dan Horton  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

The project aims to make fundamental advances in understanding how viruses interact within shared hosts using an important vector-borne pathogen. Bluetongue virus (BTV) and other species of the genus orbivirus are highly relevant insect-borne viruses of livestock. For segmented viruses such as the orbiviruses (BTV; African horsesickness virus (AHSV)), genome segment exchange (reassortment) between different strains of the same virus species is a major driver of viral diversity. For reassortment to occur two different BTV strains must coinfect the same cell either in the mammalian or insect host. Coinfection of one host by multiple viruses have been shown to either lead to viral interference/exclusion, enhancement or neutral coexistence with direct implications for the likelihood of reassortment, viral diversity and emergence of new strains. We have recently developed new molecular assays to demonstrate that BTV can exclude a second BTV strain from superinfecting natural host cells during asynchronous infections. Superinfection exclusion (SIE) will greatly affect the window of opportunity for reassortment, yet specific mechanisms, and if this is a BTV-wide phenomenon, are unknown.

Within this project the student will further elucidate the interactions between orbiviruses during coinfection of mammalian and insect host cells to critically enhance our understanding of viral reassortment, selection and host restriction. Initially we will investigate the dynamics of coinfection during synchronous and asynchronous infection time-courses across a variety of BTV serotypes and strains and ultimately across heterologous orbiviruses. The project will then investigate the specific mechanisms of virus-virus interactions observed with a focus on the generation of reassortments and viral population diversity. The generated data will then be further utilised to model viral community interactions and viral population adaptation.

The project combines multiple disciplines of molecular virology, next-generation sequencing, cell biology and bioinformatics, allowing the successful candidate ample opportunities to develop specific research directions of interest and scientific independence, while benefitting from unique scientific environments and complementary skills and facilities available at the Pirbright Institute and the University of Surrey. The successful candidate will be part of highly collaborative and vibrant research environments at both institutions, while investigating an exciting research hypothesis with strong implications for the epidemiology and evolution of orbiviruses, with direct transferability to other segmented viruses.

To carry out the laboratory part of the project, the student will initially be based primarily at The Pirbright Institute. For the data analysis and bioinformatics aspect of the project, the student will spend significant time at the School of Veterinary Medicine, University of Surrey. The two research facilities are only five miles apart, thereby making this truly collaborative project highly feasible. 

TO APPLY:  For full project details and how to apply please visit our website Studentships 2021 | The Pirbright Institute

For informal enquiries regarding this project please contact the project supervisors noted above.

For enquiries regarding eligibility and the application process please email [Email Address Removed]

For Home student eligibility guidelines, please refer to the UKRI Full Eligibility Criteria (Annex One): UKRI-030221-Guidance-International-Eligibility-Implementation-training-grant-holders-V2.pdf

Biological Sciences (4) Veterinary Sciences (35)

Funding Notes

3.5 year fully funded studentship open to UK nationals with, or who anticipate obtaining, at least 2.1 or equivalent in relevant biological subject in undergraduate degree, or a Masters degree, subject to university regulations. Students will receive stipend £15,609 pa plus allowance £2,200 pa. University tuition fees will be paid at the Home rate. EU and international applicants are welcome to apply, however will be liable for tuition fees at the international rate and must be able to fund the difference between Home and Overseas tuition fees themselves. For Home student eligibility guidelines refer to UKRI Full Eligibility Criteria above.

References

“Widespread Reassortment Shapes the Evolution and Epidemiology of Bluetongue Virus following European Invasion”. Nomikou K, et al. PLoS Pathog. 2015 Aug 7;11(8):e1005056.
“Diversity of Transmission Outcomes Following Co-Infection of Sheep with Strains of Bluetongue Virus Serotype 1 and 8”. Veronesi E et.al. Microorganisms 2020 Jun 5;8(6):851.
“An Early Block in the Replication of the Atypical Bluetongue Virus Serotype 26 in Culicoides Cells Is Determined by Its Capsid Proteins”. M. Guimerà Busquets et.al. Viruses 2021, 13(5), 919; https://doi.org/10.3390/v13050919
“Genetic analysis of a rabies virus host shift event reveals within-host viral dynamics in a new host”. Marston DA, Horton DL, Nunez J, Ellis RJ, Orton RJ, Johnson N, Banyard AC, McElhinney LM, Freuling CM, Fırat M, Ünal N, Müller T, de Lamballerie X, Fooks AR. Virus Evol. 2017 Dec 13;3(2):vex038.