Sustainable growth of the poultry industry as major source of proteins provided by the eggs and poultry meat is critical for the global food security. A major challenge for this comes from a plethora of diseases, particularly those caused by a number of major avian viral pathogens. Among the avian diseases, neoplastic diseases (cancers) induced by pathogens such as Marek’s disease, avian leukosis and reticuloendotheliosis viruses (MDV, ALV and REV) are hugely important both in relation to economic losses and animal welfare. As has been demonstrated in a number of classical examples, these diseases are also valuable models for unravelling molecular mechanisms in the induction of cancer. In the Viral Oncogenesis group, our research is focused on examining the molecular interactions between oncogenic viruses and their target avian hosts to help understand the complex pathways that drive the transformation of a normal cell into a cancer cell. Genetic diversity of avian pathogens, including oncogenic viruses, remains a major challenge in developing sustainable control strategy. Better understanding of the factors that drive viral diversity, including those from currently used vaccines, is also a major research interest of the group.
Aligned to the Avian Viral Diseases (AVD) programme grant objectives, the major aims of the group are to understand (1) the functions of the viral genes that contribute to the oncogenicity and other biological features of avian oncogenic viruses, (2) the nature of the virus-host interactions associated with viral pathogenesis, and (3) the features of the avian immune system that enable it to respond to oncogenic virus infection or to the different types of vaccines.
Currently the major focus of research is on Marek's disease (MD), a highly contagious T-cell lymphoma in poultry caused by MDV, a member of the family Herpesviridae. Through the application of reverse genetics on full length genomes of MDV cloned in bacterial artificial chromosome (BAC) vectors, we examine the functions of viral genes both in vitro and in vivo. Using excellent models of Marek’s disease induced by wild type and modified viruses in the target chicken hosts, we study the dynamic changes in the genome, epigenome, transcriptome, proteome etc. to gain insights into the molecular virus-host interactions.
As one of the first examples of vaccines against cancer, MD vaccines have been used successfully worldwide for more than 40 years. However, despite its efficacy in protecting against the disease, MDV strains continued to show increase in virulence, challenging the sustainability of the vaccination strategy. Group’s research efforts in this area include investigation into the role of vaccines in driving virulence and developing novel vaccines and intervention strategies for control.
Research focus on other oncogenic viruses ALV and REV is also to ascertain the viral determinants of pathogenicity and genetic susceptibility to infection, as well as to determine the virus-host interaction in relation to virus-induced oncogenesis.
- Most of the research on MD to identify the viral determinants of pathogenesis, virus-host interactions and immune response is carried out as part of the AVD Strategic Programme Grant (BB/J00448/1) (2012-17).
- Defra-funded project (OD0722) on Marek's disease is aimed at gaining better understanding of the basis of cell-free virus production and in developing recombinant vaccines based on novel vectors (2013-17).
- As part of the strategic Longer and Larger grant (BB/K002465/1) with partners at Imperial College London, St. Georges, Cambridge University and Roslin Institute on Developing rapid responses to emerging virus infections of Poultry, we aim to identify the molecular determinants of resistance of cell lines to MDV (2013-18).
- Under the BBSRC-funded Animal health and Welfare (ANIHWA) ERA-Net project (BB/LK014262/1) on Marek's Disease Virus induced immunosuppression, we aim to study the immunosuppressive effects of Marek’s disease vaccination (2014-17).
- As part of the joint BBSRC-NIH funded project ‘Vaccines as drivers of disease emergence’ project (BB/K011057/1), we investigate the role of currently used Marek’s disease vaccines in driving virulence of MDV strains (2013-17).
Avian oncogenic viruses such as avian leukosis and Marek’s disease viruses are major causes of cancer in chickens worldwide. With major economic losses and welfare implications, controlling these diseases are critical for sustainable growth and increased productivity of the poultry industry. Our research in this area that led to the eradication on avian leukosis virus belonging to the subgroup J from UK primary breeder flocks has helped safeguarding an estimated 3,200 jobs and £400m. Similarly, our research on Marek’s disease in collaboration with the poultry industry has led to the development of rapid test to identify and quantitate pathogenic and vaccine strains from the samples taken from birds of poultry house dust (www.bbsrc.ac.uk/research/impact/rapid-test-poultry-disease/). This technology is used widely in environmental monitoring and determining vaccination status of poultry farms.