Research Project Database
Code: EMIDA9
Title: MADISPREAD - Marek's Disease Virus Spread: In and Out of Chicken.
Country: United Kingdom
France
Germany
Funding Organisation: Biotechnology and Biological Science Research Council (BBSRC)
French National Research Agency (ANR)
Federal Ministry of Education and Research (BMBF, Germany)
Animal Group: Chickens
Pathogen: Marek's disease virus (MDV)
Mardiviruses
Disease: Marek's disease
Category: Infection, immunity and biotechnology > Fundamental/basic and Applied studies, including molecular, cellular, pathogen population dynamics and ecology > Host-Pathogen interactions (including immunomodulation and immune evasion)
Infection, immunity and biotechnology > Fundamental/basic and Applied studies, including molecular, cellular, pathogen population dynamics and ecology > Virology
Research Organisation: Ludwig-Maximilians University Munich
INRA - Institut National de la Recherche Agronomique
Free University of Berlin
Lohmann Animal Health GmbH & Co
Institute for Animal Health (IAH) Pirbright Laboratory
Number of Research Staff (FTE):  
Principal Investigator (PI): Jean-François VAUTHEROT, INRA, France
Cost (Euros): 1892844
End Date (dd/mm/yyyy): 31-12-2013
Duration (months): 36
Link:  
Project objectives and deliverables with estimated delivery dates for each deliverable (if possible): The objective of Madispread is to develop fundamental knowledge on Marek’s disease virus (MDV) entry, shedding and immune prophylaxis in order to improve the control of a major viral pathogen. The main focus is on the prevention of MDV evolution toward increased pathogenicity, arguably the most important feature of this virus that has constantly jeopardized its control.
By addressing virus entry, shedding, and control of the latter by vaccination, we aim at answering to important questions on i) the interaction between MDV and differentiated cells mediating virus entry (hematopoietic lineage) or shedding (ectodermal lineage) and ii) the rationale to design vaccines, which protect against tumour development but also reduce virulent virus spread.
Entry is defined as the step at which “infectious material” is delivered to the first target cell, in which MDV will replicate and be further transmitted to others cells. Entry presumably takes place in the lung and involves highly differentiated cells of the hematopoietic lineage (macrophages/B cells). Shedding is the stage at which infectious material is produced at the dermo-epidermal level, here again by highly differentiated cells of the ectodermal lineage.
To study virus/cell interaction, we will make use of the two existing possibilities to obtain differentiated cells, either using direct ex vivo explants from animals or embryos (WP1-WP3) or by differentiation from pluripotent chicken embryonic stem (cES) cells (WP1 & 2). The development of these new in vitro cell culture systems will make use of the most recent tools available (cytokines, growth factors and genes involved in differentiation pathways) to maintain explanted cells in a differentiated state or promote differentiation in cES cells. Emphasis will be put on transcriptomic analyses as a tool for the description of cellular gene arrays of major importance in the initial replication of MDV in macrophages/B lymphocytes and in “productive” replication of MDV in ectodermal cells. The development of in vitro cell culture systems for the above mentioned differentiated cells will allow functional studies to confirm the transcriptomic data.
As virulent virus shedding from vaccinated birds appears to be an important factor in the evolution of MDV toward increased pathogenicity, we also aim at developing and testing novel vaccines (WP4), which are designed to control shedding of virulent viruses. The working hypothesis is that if current vaccines lack the ability to spread from bird to bird, this propensity might be of importance in interfering with or protecting against virulent virus shedding. Recent functional analysis of viral genes showed that attenuation of virulence may be dissociated from shedding, and we will analyse whether such genetically modified avirulent viruses retain a good anti-tumour activity while reducing virulent virus shedding in vaccinated birds.
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