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Bluetongue virus exploits transkingdom interactions between virus-bacteria-insect and ruminant host to enhance infection


Project Description

Increasing evidence demonstrates that certain viruses can exploit bacteria or bacterial products to enhance their infectivity, replication and transmission. An exciting PhD project at the Pirbright Institute/University of Edinburgh is available to a highly motivated student with a keen interest in virology, immunology and cell-biology to investigate if transkingdom interactions between bacteria and viruses play a vital role during the infection and transmission cycle of vector-borne viruses.

Bluetongue virus (BTV) causes an economically highly significant haemorrhagic disease of ruminants and is transmitted to its mammalian host during blood feeding of its insect vector Culicoides biting midges. Within ruminants BTV replicates in a wide range of target cells, including phagocytic cells such as monocytes and dendritic cells. We have previously demonstrated that bacterial lipopolysaccharides (LPS) enhance BTV infection of bovine monocytes but not lymphocytes. LPS is present within Culicoides secreted saliva, providing the intriguing hypothesis that BTV might utilise bacterial products, provided by the insect vector or present during co-infections in the ruminant host, to enhance cell infection.

Within this project we will initially characterise if bacterial products facilitate BTV infection of monocytes through direct (e.g. increased virus-receptor binding, enhanced virus stability, increased virus uptake through virus aggregation) or indirect (e.g. immunemodulatory) mechanisms. The project will then expand to elucidate if bacterial products enhance BTV infection in other natural primary target cells, including those draining the skin, and if specific interaction between bacteria and BTV vary across strains from divergent serotypes as well as virus particle types (whole virus, infectious subviral particle (ISVP)).

Potential interaction of bacteria and virus in the context of vector-borne viruses will add further complexity to the already intriguing host-vector-virus interface and project outcomes will be of great interest to other vector-borne viruses including those transmitted to humans.

The successful candidate will be trained to apply a wide range of key virological and immunological technologies such as flow cytometry, immunofluorescence microscopy, electron microscopy, molecular viral diagnostics, primary cell infectivity assays, handling of vector insects and statistical analysis. The student will join a vibrant, multidisciplinary and highly collaborative research environment and be highly encouraged to develop specific aspects of the project depending on their own scientific interest. The candidate will further learn to communicate their own research as part of regular lab meetings and attendance of national/international conferences and writing of peer-reviewed publication. All students at The Pirbright Institute and the Roslin Institute/University of Edinburgh are also greatly encouraged to participate in other development activities such as regular attendance of internal and external seminars, training courses, journal clubs and scientific outreach.

Funding Notes

This is a fully funded studentship open to science graduates (with or who anticipate obtaining at least 2.1 or equivalent in a relevant biological subject in an undergraduate degree, or a Masters degree - subject to university regulations). Open to UK students and eligible EU students who qualify for home-rated fees in line with UKRI Residential Guidelines - Visit Website for details. Eligible students will receive a minimum annual stipend of £15,009; university registration fees will be paid. Students without English as first language must provide evidence of IELTS score of 7.0, no less than 6.5 in subsections.

References

1. Erickson et al., 2018, Cell Host & Microbe 23, 77–88
2. Stevens et.al. 2019 accepted Journal of General Virology
3. Darpel et.al. 2011 PloSOne 2011 Mar 14;6(3):e17545

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