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Analysis of the molecular mechanisms of tumour induction and genetic control of subgroup J avian leukosis virus in chickens - OD0716

Description
Chicken is one of the leading sources of protein in the world. With approximately 30 million broiler chickens produced annually, diseases affecting these meat-producing birds have serious consequences on the economy and welfare of birds. Among the various pathogens that affect poultry health, oncogenic viruuses are considered very important due to their widespread nature, ability to persist and produce high levels of mortality. Avian leukosis viruses (ALV) are an important group of pathogens associated with the induction of a variety of neoplastic diseases in poultry. Although ALV inefctions have been brought under control through eradication programmes in the last 30 years, the sudden emergence of an ALV belonging to a new subgroup J (ALV-J) and its rapid spread worldwide had devastating consquences on the poultry industry and welfare of birds. Pioneering research on ALV-J induced disease in the last ten years in our groupp at the Institute for Animal Health, Compton (partly fundeed through DEFRA funded projects OD0703 and OD0708) has elucidated several unique aspects of this new virus. These include (a) their occurence mainly in the meat-type chickens, where it induces tolerance and persistent viraemia (b) their unique genome structure with a distinct env gene possibly by recombinantion (c) their ability to undergo rapid sequence and antigenic variation (d) their increased potential to genrate acutley trnsforming viruses, mainly by transduction of the myc oncogene, and (e) their capability to induce tumours of the myeloid lineage.
This new proposal is a continuation of the previous DEFRA-fundeed projects, with the research objectives derived from the observations and findings of the previous studies. As mentioned before, one of the unique features of ALV-J is ability to induce tumours of the myeloid lineage compared to the more common lymphoid lineage induced by other ALV subgroups. We would like to examine the basis for the unique tropism for the myeloid leukaemogenicity of these virus isolates. As part of our studies on genetic resistance to ALV-J induced tumours in different genetic lines of chickens, we have noted that the oncogenicity of ALV-J were not suprisingly not very high in line 151, a line of chicken often regarded as highly susceptible to tumour formation to other highly susceptibly to tumours by ALV-A were highly susceptible to ALV-J-induced tumours. We would like to investigate the basis for the sub group-specific resistance amoung inbred lines of chicken.

The objectives of the project are to provide an understanding of the basis for oncogenicity and genetic susceptibilty to ALV-J induced tumours. Identifcation of the determinants of oncogenicity and genetic resistance to ALV-J-induced tumours could help in examining alternative strategies of controlling the infectous and the effects of the disease. As there are no vaccination strategies of the control of ALV-induced infections, the findings from these studies could provide the basis for improving resistance of birds to the disease, and form a valuable adjunct to the current control strategies that are mostly based on eradication of the virus by removing the infected birds.

The objectives of the project are consistent with DEFRA`s research requirement R22 (investigations of the molecular mechanisms of tumour induction and genetic control of Avian Leukosis Virus subgroup J aimed at recommending sustainable control measures of the pathogen for the production of domestic chickens). In addition, this work will contribute to the scientific knowledge for the control of this economically important disease and help improving poultry welfare. The project would also help to maintain scientic expertise in studying these diseases that are vital for control of possible emergence of such new viruses in the future. Furthermore, the studies will contribute to the improvement of poultry health and welfare that will increase the effectiveness to other vaccinations reducing the need for pharmaceutical control of other infections. In addition, the identification of genetic factors that determine resistance to tumours could have harnessed for selective breeding programmes. All these benefits will certainly contribute to the increased competitiveness of the UK poultry industry as well as imporved product quality for the consumer avoiding unwanted pathogens in the food chain. Thus, the proposed work would contribute to provide sustainable means of control that can be used to ensure a continued supply of wholesome poultry meat to the human chain.
Objective
01: Comparion of the kinetics of infection, virus load and integration sites in line 0 and line 151 chickens infected with HPRS-103 and examine the correlation with tumour induction.
02: Investigate the role of the E (XSR) element in the ALV-J genome in the induction of tumours.
03: Examine the cell tropism and mechanisms of oncogenicity of chimaeric HPRS-103 virus that differ in the env gene.
04: Identification of factors associated with the generation of acutely transforming viruses from tumours induced by wildtype and chimaeric ALV-J viruses.
Project Documents
• FRP - Final Report : OD0716 Final report   (551k)
Time-Scale and Cost
From: 2003

To: 2009

Cost: £235,880
Contractor / Funded Organisations
Institute for Animal Health (BBSRC)
Keywords
Animal Diseases              
Animal Health              
Biotechnology              
Control              
GM Non-Food              
Neoplastic              
Pathogenesis              
Plants and Animals              
Poultry              
Fields of Study
Animal Health