Marek's disease virus spread: In and out of chickens
Lead Research Organisation:
The Pirbright Institute
Department Name: Avian Infectious Diseases
Abstract
Marek's disease (MD) is a highly contagious virus-induced lymphoma in poultry caused by Marek's disease virus (MDV), an alphaherpesvirus heavily affecting chicken industry. In spite of the widespread use of live attenuated vaccines during the last 40 years, MD remains a major threat for poultry production with estimated annual economic losses in the range of 1 billion dollars worldwide. In Europe as well as in other countries, MDV has evolved towards a substantially increased virulence observed in more recent strains, thereby threatening the sustainability of the current vaccination strategy. The endemic nature of the disease is clearly linked to the mode of virus transmission and to incomplete protection provided by current vaccines. It is well known that while vaccines protect against the disease, infection and virus shedding are not halted. We hypothesize that the persistence and bird-to-bird transmission of pathogenic strains in vaccinated birds provide the basis for the emergence of very virulent strains. Successful transmission of MDV entails efficient viral shedding from infected birds and the entry of the virus via the respiratory route, in both vaccinated and naïve birds. Improved knowledge about these two essential steps in virus replication is critical to ultimately reduce MDV contamination of the environment and infection of the animals. To date, entry and shedding of MDV in vivo have been poorly studied compared to virus-induced tumourigenesis, host resistance and virulence. Our project aims to study the key elements on the cellular and molecular levels that are involved in virus entry and shedding. The novelty of our project is to focus on differentiated cells, which represent the major target cells infected in vivo and are derived either from the haematopoeitic lineage (macrophages and lymphocytes) or from the skin epithelium.
Technical Summary
Marek's disease is a major disease of poultry that induces major economic and welfare implications for poultry health. Despite the widespread vaccination for the last 40 years, the threat from the disease has not disappeared, as the viral strains continue to increase in virulence. The proposed project aims at generating underpinning knowledge on the keystone of MDV entry and shedding and at defining its interaction with and replication in differentiated cells from the hematopoeitic (macrophages and lymphocytes) and from the skin epithelium lineages. the feather follicle epithelium is the only site in the infected chickens where a fully productive infection of the virus resulting in the continuous shedding of the virus occurs. At the same time the lymphocytes from the infected birds carry a latent infection with very limited expression of viral antigens. Our preliminary studies have also suggested a direct correlation between virus virulence and the levels of replication in the feather follicle, with highly virulent strains replicating at higher levels resulting in increased shedding. The project will aim to exploit the current knowledge on avian cell differentiation (with an emphasis on skin and lymphoid lineages), type-specific cellular determinants controlling MDV spread and shedding and on the vaccines that control shedding and entry of pathogenic MDV strains to develop viable and cost-effective alternative to primary avian cells for vaccine production and virus studies, and improve vaccine efficacy in the control of spread and shedding of pathogenic viruses. By studying virus entry and shedding, we aim at promoting sustainable methods to reduce MDV endemics and to improve biosecurity by generating vaccines with improved efficiency regarding the reduction of environmental contamination by MDV.
Planned Impact
By targeting viral spread, which is essential for viral persistence in vaccinated flocks, our project aims at developing novel control strategies, which will reduce MD in poultry and create conditions in which the emergence of MDV with increased virulence can be stopped. A better knowledge of the conditions in which a virus contaminates naïve or vaccinated sentinel birds is a prerequisite to the development of sustainable methods to reduce the impact of MD that is endemic worldwide. From our research into cellular elements that are essential for virus production in skin, 'favourable' genotypes of chickens could be selected that would show reduced shedding of virus. A vaccine that would induce a 'sterile immunity' would also prevent contamination of the environment by virulent viruses. Infections with Marek's disease virus (MDV) have a high economic impact worldwide and the prevention strategies employed universally rely on vaccination of chickens either in ovo or at 1-day-old. The chicken industry in all of Europe is a tightly interwoven net with respect to the use of only a small number of different chicken breeds, farm structures, and management regimens applied. Therefore, national approaches to improve control of MDV and perform state-of-the art research on the continually evolving pathogen would seem unreasonable. The rationale for the joining of forces of the premier scientists and national research centers with one of the most prominent companies providing broiler as well as layer breeds in Europe and beyond was the driving force for this consortium that has worked together over more than a decade now. Who will benefit from this research? The proposed research will benefit the poultry industry as an improved understanding of the molecular mechanisms of MDV spread could lead to new strategies of designing new vaccine. Judging from the interest in the lay press, there is a considerable interest among the public for the scientific understanding of how some diseases produce damage to animal health. This proposal could unravel some of the intricate pathways of cancer in animals, and hence will have significant impact on animal welfare through all poultry production systems. What will be done to ensure that they have the opportunity to benefit from this research? A special attention will be paid to the exploitation of results as this project will identify genes, molecular and cellular mechanisms which may be at the origin of industrial developments. A consortium agreement will be engaged and negotiated through the institutional representative of each partner. This consortium agreement will follow the frame described in annex 5, with a particular focus on i) confidentiality as the developments in WP1 and 2 will engage the exchange of confidential information and ii) exploitation of the results, as commercial exploitation may concern either new cell-culture systems for the production of vaccines or the design of more efficient vaccines. Identification of genes/pathways/molecular mechanisms (WP1-2-3) may lead to the application for joined patent(s) in conditions that will have to be defined in the IPR section of the consortium agreement. Material rights may concern cell-lines or vaccines which may arise as breakthrough developments from WP1 - 2 and 4. The project aims mainly to target the poultry vaccine market with a promising new offer in MDV replication process that can be monitored in vitro and therefore that can lead to a better production and control of the poultry vaccines.
People |
ORCID iD |
Venugopal Nair (Principal Investigator) |
Description | This project is operated together with a number of EU partners. The major objective of the grant for which the PI is responsible is to examine the molecular changes in the skin of birds infected with Marek's disease virus (MDV). The virus-host interaction in the feather follicle epithelium is unique, as it is the only cell type where virus completes fully productive infection. As part of this project, we held two meetings: one inaugural meeting in Paris and a progress meeting in London. Preliminary experiments using recombinant MDV expressing UL47GFP have indicated that the expression of UL47 is unique to the feather follicle epithelial cells from where the virus is shed. Further studies to understand the dynamics of MDV infection in the epithelial cultures using skin organ culture model. |
Exploitation Route | Commercial opportunities for novel control approaches over and above the current vaccination method/ Understanding the molecular mechanisms of cell free virus production and spread of the virus from the skin can help in developing novel strategies to prevent virus spread. |
Sectors | Agriculture Food and Drink |
Description | The findings of the project have significantly advanced our understanding of the transmission biology of Marek's disease virus infection |
First Year Of Impact | 2015 |
Sector | Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | Marek's Disease Virus induced immunosuppression |
Amount | £395,000 (GBP) |
Funding ID | BB/LK014262/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2014 |
End | 09/2017 |
Description | OIE Reference Laboratory |
Organisation | World Organisation for Animal Health, France |
Country | France |
Sector | Public |
PI Contribution | As the Reference Lab, we have contributed to the diagnostic procedures and preparation of manual |
Collaborator Contribution | Collaborators has published our activities and prepared the book |
Impact | Publication of the Manual on diagnostic tests |
Description | AN INTERVIEW WITH PROFESSOR VENUGOPAL NAIR |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Professor Venugopal Nair is a Research Group Leader at The Pirbright Institute, a visiting Professor of Avian Virology at the Department of Zoology, and a Jenner Investigator at the Jenner Institute, University of Oxford. He is also a member of the Microbiology Society, and in this interview, he tells us more about his research into viral diseases of livestock. |
Year(s) Of Engagement Activity | 2020 |
URL | https://microbiologysociety.org/membership/meet-our-members/focus-area-viruses/an-interview-with-pro... |
Description | Avian Genetics and Immunity (University of Surrey) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | The Symposium on Avian Genetics and Immunity is being to engage international audience with interests on avian genetics and immunity |
Year(s) Of Engagement Activity | 2017 |
URL | http://geneticsandimmunity.com |
Description | Chaired the Poultry Disease group meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Poultry Disease group is a forum of veterinary practitioners to discuss the advances in poultry diseases that could be translated from research labs to the farms |
Year(s) Of Engagement Activity | 2017 |
Description | Conor Haydon participated in the STEM Day - Speed interviews and Careers Day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | STEM day engagement and careers |
Year(s) Of Engagement Activity | 2018 |
Description | Inauguration of the UK-China Centre of Excellence for Research on Avian Diseases (CERAD) and Symposium on Recent Advances in Avian Disease Research |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Inauguration of the UK-China Centre of Excellence for Research on Avian Diseases (CERAD) and Symposium on Recent Advances in Avian Disease Research. This was held in Binzhou, Shandong province in China in 2015 |
Year(s) Of Engagement Activity | 2015 |
Description | Invited talk at the National Institute for Animal Biotechnology, Hyderabad on 3rd Jan 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Participants were engaged in the recent advances in biotechnology, challenges and opportunities. |
Year(s) Of Engagement Activity | 2019 |
Description | Poultry Health Course (Pirbright) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | The course is organised for participants from Brazil to understand the current advances in poultry diseases. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.poultryhealthcourse.com/ |
Description | Presentation on the effects on oncogenic virus infection at the Veterinarian's Forum, Namakkal, India on 29 Dec 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | The purpose of the engagement was to update the practicing poultry veterinarians on the problems with oncogenic virus diseases and methods of control. The meeting attended by nearly 100 veterinarians was very informative and ended with a long discussion on the challenges and innovations |
Year(s) Of Engagement Activity | 2018 |
Description | Second Symposium of the UK-China Centre of Excellence for Research on Avian Diseases held in March 2016 in Binzhou, Shandong Province, China |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The second international meeting of the UK-China CERAD was attended by a number of delegates from both UK and China and reviewed the progress. Plans were drawn of further activities and plans for securing additional grants. |
Year(s) Of Engagement Activity | 2016 |
Description | Sue Baigent participated in the Teen Tech event on 22nd Jan 2019 on General Science engagement |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | A General Science event |
Year(s) Of Engagement Activity | 2019 |
Description | Sue Baigent participated in the Winston Churchill Careers Fair on 7th Nov 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Careers fair |
Year(s) Of Engagement Activity | 2018 |
Description | University of Surrey School of Veterinary Medicine Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Presentation of work conducted at The Pirbright Institute |
Year(s) Of Engagement Activity | 2016,2017 |
Description | V Nair invited to talk on 'Cell type- and disease stage-specific interactions of Marek's disease virus & the host' at the International Symposium on Marek's disease and avain herpesiviruses at Yangzhou, China during 29th July to 2nd Aug 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Most recent updates in the field of avian herpesvirus research was discussed and active engagements for future collaborations discussed |
Year(s) Of Engagement Activity | 2018 |
Description | V Nair was invited to talk a the Poultry Health Workshop and Conference on 19th-20th Nov, 2018 in Kathmandu, Nepal |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | more than 100 stakeholders from different sectors of the Poultry industry and academia attended the meeting. There was engagement from the different sectors for initiating a combined approach for finding solutions |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.cmdn.org. |