Functional analysis of novel microRNAs encoded by avian herpesviruses

Lead Research Organisation: The Pirbright Institute
Department Name: Avian Infectious Diseases

Abstract

Marek's disease (MD) is a common disease of chickens involving paralysis and commonly death from the growth of highly malignant T lymphomas (cancers of white blood cells). MD is caused by a transmissible agent, Marek's disease virus (MDV). MDV is very contagious and is a major threat to the poultry industry worldwide. Presently, it is controlled by vaccination, and nearly 22 billion vaccine doses a year are used in an attempt to control the disease. Despite this, there is a continuous evolution of the virus towards greater virulence necessitating the introduction of new vaccines at regular intervals of 8-10 years when the previous generation of vaccine becomes ineffective. The mechanisms by which the virus gains virulence and produces tumours remain very poorly understood. During the last 2 years, with the financial support from the BBSRC, we have been examining the role of novel regulatory molecules called microRNAs (small 22-nucleotide long RNA molecules) encoded by the virus and the host in inducing MD. As part of this grant, we have identified several novel microRNAs in the genome of the 3 members of the genus Mardivirus. Preliminary studies have indicated that these tiny molecules are produced at very high levels in MDV-induced cancer cells and their deletion from the virus genome affected their ability to produce tumours. In this proposal, which is aimed to build on the findings of our work, we want to continue our research to identify the molecules targeted by the virus-encoded miRNAs and examine the effect of deleting these microRNAs from the genomes of these viruses.

Technical Summary

This proposal is aimed primarily to continue the work onging as part of a BBSRC funded project to examine the role of Marek's disease virus-encoded micro RNAs in the pathogenicity of Marek's disease, a highly contagious neoplastic disease of poultry characterised by the development of rapid-onset lymphomas. As part of this project, we have identified several novel microRNAs encoded by the members of the genus Mardivirus including 13 in MDV-1, 17 in MDV-2 and 11 in herpesvirus of turkeys (HVT), a vaccine strain closely related to MDV-1 and MDV-2. All these microRNAs are expressed at very high levels in infected/transformed cells, suggesting a direct role for these microRNAs in the biology of the virus infection and disease. In this proposal, we aim to carry out detailed examination of the targets for these microRNAs, analyse their expression in MDV-transformed cell lines/tumours and finally use the reverse genetics system of bacterial artificial chromosome (BAC) clones of the 3 serotypes to examine the role in the natural target host disease models.

Publications

10 25 50
 
Description The research project has developed a significant amount of data on microRNA expression profiles in a number of avian cell lines of B lymphocyte, T-lymphocyte, Macrophage and embryonic stem cell origin. In addition, the project has helped to identify novel microRNAs encoded by different avian herpesviruses, including the duck enteritis virus. These datasets are valuable for further studies to understand the functional significance of microRNA-mediated gene regulation.
Exploitation Route The finding from the project and questions that have arisen from the project has led to the successful winning of a new BBSRC grant to study the cistrome and transcriptome of avian tumours.
Sectors Agriculture

Food and Drink

 
Description Defining the cistrome and quantitative transcriptome of virus-transformed cells 12. BB/I014284/1 'Defining the cistrome and quantitative transcriptome of virus-transformed cells'- New grant funded by BBSRC April 2012- March 2015 (£548K).
Amount £548,000 (GBP)
Funding ID BB/I014284/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2012 
End 03/2015
 
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 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 Invitation to give keynote talk on 'Control of avian diseases: Challenges and opportunities' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave the Keynote talk on 'Control of avian diseases: Challenges and opportunities' at this International Symposium organized with an aim to gather international virology experts from both human and veterinary fields to share research experience, update findings and contribute their expertise through presentation and interactive discussion. The topics will cover a wide range of virology research common in both human and animal aspects. In addition, technological platforms such as vaccine development, and novel assays will be emphasized and addressed.
Year(s) Of Engagement Activity 2018
URL http://www.biotec.or.th/virus-symposium2018/index.php
 
Description Invited to talk at the International Conference on Building Human and Animal Health Capacities organised by the Jordan University of Science and Technology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Participated in the discussion and talked on 'The recent advances in vaccination-based control of poultry diseases'. The need for increased awareness of the pathogen diversity in the design of vaccines and the opportunities from advances in vaccine technologies were discussed
Year(s) Of Engagement Activity 2017
URL http://www.just.edu.jo/conferences/bhahc/Pages/default.aspx
 
Description Organised the 3rd UK-China CERAD meeting in Guildford, UK in July 2017 
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 3rd UK-China CERAD meeting helped to bring together professional from both countries to identify challenges and exploit the opportunities for improved control of poultry diseases and increasing food security.
Year(s) Of Engagement Activity 2017
URL http://www.uk-china-cerad.org/
 
Description Organising and giving Keynote talk at the GARAD meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Global Alliance of Poultry industry professional and academia to discuss about the advances in control strategies of diseases
Year(s) Of Engagement Activity 2018
URL http://Garad.org
 
Description Poultry Health course 
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 Poultry Health Course is run as a residential and online course to transfer recent advances in avian disease research from the laboratory to the field.
Year(s) Of Engagement Activity Pre-2006
URL http://www.poultryhealthcourse.com/
 
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 UK-Malaysia Vaccinology Workshop (Malaysia) 
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 This workshop aimed to build long-term and sustainable links between scientists in the UK and Malaysia working on/have interests in veterinary vaccines. This workshop has encouraged early career researchers from veterinary, biological and social sciences to understand the ever-increasing threats to global food security from infectious animal diseases and their control using next generation vaccine strategies.
Year(s) Of Engagement Activity 2016
URL http://ukmalaysiaworkshop.co.uk/
 
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