UK-China partnership on Global Food Security: Combating avian tumor diseases for sustainable poultry production

Infectious diseases result in direct and indirect losses at various steps of poultry farming and amongst them neoplastic disease caused by viruses is a major economic problem faced by the poultry industry worldwide. The oncogenic viruses causing neoplastic infection in chickens are herpesviruses comprising of Marek's disease virus (MDV) and retroviruses comprising of reticuloendotheliosis virus (REV) and avian leucosis virus (ALV). ALV is the most common naturally occurring avian retrovirus that can cause a variety of neoplastic disease conditions in chickens. In addition to causing neoplasia, ALV is known to be associated with reduced productivity and other production problems in affected flocks. Based on the properties of viral envelope glycoproteins, ALV is classified into six subgroups: A, B, C, D, E and J. Originally isolated by the Pirbright Institute in the late 1980s, ALV-J spreads widely and induces myeloid leukosis and a broad spectrum of additional disorders, such as histiocytic sarcoma, hemangiomas and erythroblastosis. The original strains have almost been eradicated from most of the commercial poultry flocks in Europe and the United States but in Asia, the virus evolved into a great variety and recently emerging Chinese isolates coarsely induce various tumours in both commercial laying hen flocks as well as native Chinese breeds of chickens. Defining the molecular background of the tumorigenesisis is needed to develop more effective control and eradication programmes in China. In this proposal, we aim to obtain detailed comprehensive picture on the molecular events to understand and predict the molecular pathways to ALV-J induced cancer. This includes non-coding RNA profiling for the role of non-coding RNAs in ALV-J induced oncogenesis, oncogene myc targetome identification and the role of myc-binding in maintaining the transformed phenotype and myc knockout by CRISPR/Cas9 system for the role of myc in maintaining the transformed phenotype. As the co-infection of ALV-J with other tumor viruses such as Marek's disease virus and Reticuloendotheliosis virus is very common and caused more serious pathogenic effects, we are going to elucidate the synergistic mechanism of ALV-J+REV/ALV-J+MDV co-infection in vitro and in vivo. The findings will be very valuable in developing new approaches for the eradication of ALV-J in China and control of cancers caused by oncogenic viruses. We also want to establish the resistant cell line by editing ALV-J receptor NHE1 using CRISPR/Cas9 system to explore genetic resistant to ALV-J. Finally, we will develop the rapid diagnostic kits to detect ALV-J infection in the field to aid the ALV-J control and eradication in China.

Poultry industry is a rapidly growing sector crucial for the global food security, acting as a major source of protein for the growing world population. Avian leukosis viruses (ALV) are retroviruses associated with the induction of tumours of haemopoietic cells in birds. Although diseases due to ALV have largely been controlled in Europe and USA through successful eradication programmes, it continues to be a major problem in many countries including China, where it has caused serious economic losses in recent years. In particular, myeloid leukosis and other tumours due to ALV-J remains a major disease that threatens the Chinese poultry industry. Detailed understanding of the molecular basis of tumours induced by ALV-J, generation of resistant cell line, and development of rapid diagnostic tools for ALV-J detection in the field all will benefit development of new strategies for control and eradication of ALV-J in Chinese poultry industry. The beneficiaries of this research will include academic scientists, the poultry breeding companies, chicken farms, diagnostic professionals, the Pirbright Institute, the BBSRC and its stakeholders such as Defra and the UK poultry farming industry.
The research will have general impact with the wider scientific community, veterinary and medical practitioners, students and general public. Engagement with these diverse groups will be achieved via meetings, articles in the trade press, tailored web pages, press releases to the media and outreach events in schools.
In the longer term the research may lead to medical benefits by improving control of human virus pathogens which will benefit the UK MRC and UK department of Health, the pharmaceutical industry and international organization such as the World Health Organization.
If the proposed studies lead to new approaches for controlling ALV-J or other viral diseases, additional funding will be sought from relevant funding agencies and other sources for further development. There is extensive experience within the Pirbright Institute of patent applications and commercialisations, new opportunities will feed into an established system for technology development and knowledge transfer by the Pirbright Business Development group.
Rapid-onset transformation induced by myc is also a good model for studying cancers in other species including humans as myc is one of the most frequently deregulated oncogenes in human malignancies.