Location: Avian Disease and Oncology ResearchTitle: Research update: Avian Disease and Oncology Laboratory avian tumor viruses Author
Submitted to: United States Animal Health Association Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 10/18/2012
Publication Date: 10/18/2012
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. United States Animal Health Association Proceedings. 513-516.
Technical Abstract: Genomics and Immunogenetics Use of genomics to identify QTL, genes, and proteins associated with resistance to Marek’s disease. 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. Some highlights of this year’s findings include: (1) analysis of RNA seq datasets indicates both the Toll-like receptor and JAK/STAT pathways are conserved responses to MDV infection in commercial broilers and experimental layers, and genes at the start of each pathway can be selected to modulate the response, (2) Meq binds AP-1 sites to regulate expression of genes that influence immunological responses including MAPK signaling, which is also needed to maintain growth in low serum, and (3) a complete list of polymorphisms and genes in the MDV genome associated with in vitro attenuation has been compiled, and testing of recombinant MDVs indicates that a SNP in UL5 (helicase/primase) has significant impact on viral virulence. Host Genetics and Vaccinal Protective Efficacy against MD. Vaccinal protective efficacy against vv+MDV challenge was studied in MD resistant and susceptible chickens. Chickens from a MD resistant line (63) and a susceptible line (72) were either vaccinated or vaccinated followed by vv+MDV challenge. Chickens from both lines that were only vaccinated with either HVT or CVI988/Rispens did not develop any tumor and survived throughout the experiment. Chickens that vaccinated followed by vv+MDV challenge resulted in differential MD incidence and protective index (PI). Both HVT and Rispens conveyed comparable protection against the vv+MDV challenge with PI 91.2 and 86.7 percent in line 63, respectively. In comparison, CVI988/Rispens conveyed 80 percent protection while HVT achieved significantly lower protection (25%) in line 72. This result confirms our previous report that host genetics plays a vital role in modulating vaccinal protective efficacy. Furthermore, next generation RNA sequencing data suggest vaccine, MDV, and vaccine plus MDV differentially up- or down-regulated global gene expression in both MD resistant and susceptible chickens. RNA samples were collected from both MD resistant and susceptible lines either vaccinated, MDV challenged, and both. RNA libraries were constructed following standard procedures for next generation RNA sequencing with Illumina’s HiSeq platform. The RNA reads data suggested that the global gene expression differed between the MD resistant and susceptible chickens and differentially up- or down-regulated by each vaccine, MDV, or the combination of both vaccine and MDV. This finding suggests host genetics effect on vaccinal protective efficacy may be partially explained by differential globe gene expression upon va