Research update: Avian Disease and Oncology Laboratory avian tumor viruses

Authors: Fadly, Aly; Cheng, Hans; Dunn, John; Heidari, Mohammad; Hunt, Henry; Lee, Lucy; Silva, Robert; Zhang, Huanmin

Submitted to: United States Animal Health Association Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 10/4/2011
Publication Date: 7/30/2012
Citation: Fadly, A.M., Cheng, H.H., Dunn, J.R., Heidari, M., Hunt, H.D., Lee, L.F., Silva, R.F., Zhang, H. 2012. Research update: Avian Disease and Oncology Laboratory avian tumor viruses. In: Proceedings for the 115th Annual Meeting of the United States Animal Health Association, September 29-October 5, 2011, Buffalo, New York. 462-464.

Interpretive Summary:

Technical Abstract: Genomics and Immunogenetics Marek’s disease (MD), a lymphoproliferative disease caused by the highly oncogenic herpesvirus Marek's disease virus (MDV), continues to be a major disease concern to the poultry industry. The fear of MD is further enhanced by unpredictable vaccine breaks that result in devastating losses. The field of genomics offers one of the more exciting avenues for enhancing control of MD. By identifying genes that confer genetic resistance, it should become possible to select for birds with superior disease resistance. Genetic resistance to MD is a complex trait controlled by many genes. Identification of these genes is a major challenge despite the existence of the chicken genome sequence and ever increasing number of tools, especially next generation sequencing. Thus, we have been implementing and integrating genomic approaches that identify QTL, genes, and proteins that are associated with resistance to MD. The rationale for using more than one approach is that the strengths of each system can be combined to yield results of higher confidence. Another justification is that given the large volume of data produced by genomics, each method provides an additional screen to limit the number of targets to verify and characterize in future experiments. Our combined approaches of (1) sequencing of MD resistant and susceptible chicken lines to identify genomic regions under selection for MD incidence, (2) chromatin immunoprecipitation followed by sequencing (ChIP seq) to identify MDV Meq and chicken c-Jun binding sites, (3) gene expression profiling between cell lines to identify genes and pathways regulated by MDV Meq, and (4) allele-specific expression screens by RNA sequencing to identify genes with differential allele response to MDV infection have identified 97 high-confidence candidate genes that are directly regulated by MDV Meq and help explain differences in genetic resistance to MD. If confirmed, these genes and their associated genetic markers would be ideal candidate for genomic selection. Genetics Effect on Vaccine Efficacy. Since their invention, vaccines have proven to be the most effective and economical method to combat infectious diseases in humans as well as in livestock. Efforts to improve vaccine protective efficiency have continued and expanded. Host genetics differences were investigated for the influence on MD vaccine efficacy using unique genetic lines of chickens. Our data suggests that host genetics play an important role influencing MD vaccine protection efficiency. Continuous analyses of our research data further suggested that different genetic lines of chickens respond to the same one vaccine with different protective efficiency. Marek’s Disease Virus Evolves to Higher Virulence in Birds with Limited Genetic Variation. MD is still a major concern as MDV continues to evolve to higher virulence. Most studies addressing the evolution of MDV virulence have concentrated on the virus while largely ignoring the hosts’ influence. The host system called the major histocompatibility complex (MHC) represents a highly polymorphic system designed to defend the species from extinction by the fast paced evolution of a parasite. In natural chicken populations, there are hundreds of different MHC haplotypes that oscillate in response to pathogen evolution, but commercial poultry breeding has limited the number of MHC haplotypes to six or less. Our current work has shown that MDV can evolve to higher virulence in birds with a single MHC haplotype. Thus, we predict the best way to reduce the chronic problem of MD incidence in commercial chickens is to rotate the placement of MHC haplotypes similar to the simple method of crop rotation used to control pests in the field. Incorporation of this method into modern poultry production may greatly reduce future virus evolution resulting in substantial saving