Project Number: 3635-32000-016-00
Project Type: Appropriated

Start Date: Oct 01, 2011
End Date: Sep 30, 2016

Objective:
Objective 1: Identify host and/or viral genetic determinants that control pathogenicity, transmission, and drive the evolution of new strains of avian tumor viruses. Subobjective 1.2: Identify the genetic determinants in the MDV genome that account for vitro attenuation. Subobjective 1.3: Factors that influence the development of spontaneous ALV-like tumors. Subobjective 1.4: Confirming an association between MDV replication rate and pathotype. Objective 2: Develop diagnostics for detecting new strains of avian tumor viruses. Subobjective 2.1: Evaluation of MDV BAC clones as standardized reagents for MDV research. Subobjective 2.2: Surveillance for virulent strains of avian tumor viruses in field flocks and develop improved diagnostics for new strains. Subobjective 2.3: Development of reliable techniques for immunohistochemistry (IHC) using paraffin-fixed sections. Objective 3: Elucidate the genetic determinants that modulate MDV interactions with the avian immune system. Subobjective 3.1: Identification and characterization of host/viral genes that mediate production of cell-free enveloped infectious virus particles in the FFE Subobjective 3.2: Role of NK cells in vaccine-induced immunity against MD. Subobjective 3.3: Role of macrophages and T cells in viral transport to lymphoid organs and FFE. Objective 4: Discover safe and highly effective vaccine platforms that convey protection against emerging MDV strains. Subobjective 4.3: Determine protective ability of high passage levels of a BAC clone of strain Md5 of MDV containing LTR from REV. Subobjective 4.4: Evaluation of vaccine competition using HVT strains.

Approach:
Avian tumor viruses of economic importance include: 1) Marek’s disease virus (MDV), a herpesvirus that induces a lymphoproliferative disease of chickens that, in the absence of effective control measures, is capable of causing devastating losses in commercial layer and broiler flocks; and 2) avian retroviruses, namely avian leukosis virus (ALV) and reticuloendotheliosis virus (REV), both are associated with neoplastic diseases and other production problems in poultry. Also, both ALV and REV are potential contaminants of live-virus vaccines of poultry. Critical needs are: 1) better MDV vaccines to protect against the current and next generation of virulent field strains of MDV; 2) a long-term strategy designed to reduce the ongoing emergence of new virulent MDV through multiple barriers or reduction in viral load and shedding; and 3) better procedures to detect and control new ALV recombinants. The primary emphasis will be on molecular approaches to better understand which viral genes are important for immunopathogenesis and shedding of MDV. Parallel studies will monitor the virulence of field strains of MDV and avian retroviruses, primarily ALV. Studies are also aimed at characterization of new virus isolates and on improving assays for their detection; additional efforts will be devoted to better understand MDV immunity and role of MDV vaccines in enhancement of spontaneous non ALV-induced tumors. The four objectives are highly interrelated and interface in a manner that should not only identify new basic knowledge but also translate this knowledge to practical use in control programs. The end product will be a better understanding of viral gene function, virus-host interactions and the development of materials and improved methodology for diagnosis and control of avian tumor viruses.