Host Chromosome Integration Profiles of Marek’s Disease (MD) Virus and Vaccine Strains Differ Between MD Resistant and Susceptible Lines of Chicken

The causative virus for Marek’s Disease (MD) in chickens, a gallid alpha-herpesvirus (MDV), integrates randomly across the host genome and at high frequency into host telomeres in B and T lymphocytes during its highly replicative phase. Ultimately, the virus is found only in an integrated form temporally associated with latency and host cell transformation (Robinson et al. 2010, 2014). MDV-induced tumors appear to undergo a progressive selection process as early-stage tumors demonstrate a heterogeneous integration profile and late-stage tumors have a more homogenous chromosome-integration profile (Robinson et al. 2010; McPherson et al., in prep). These selective forces in tumorigenesis may be influenced by viral integration site, resulting in a suite of common or ‘preferred’ host chromosomes harboring integrated MDV among late-stage tumors. MD vaccines (Rispens, HVT, SB-1) integrate into host chromosomes, but do not establish the latency-associated virus integrated-only phenotype (McPherson et al. 2016). The current study investigated the influence of host genotype on virus- or vaccine-host genome interactions from 1-21 days post infection (dpi)). Inbred lines 6₃ (MD-resistant) and 7₂ (MD-susceptible) were challenged with oncogenic Md5 or vaccinated with Rispens or HVT; splenocytes (a mix of B and T cells) were analyzed. The resulting dynamic profiles will be discussed. Interestingly, the Md5-challenged lines were found to differ significantly in the percentage of cells demonstrating specific virus-host phenotypes. The MD-susceptible line indicated a higher percentage of cells exhibiting the latency- and transformation-associated phenotype as compared to the resistant line, and as early as 4 dpi. Supported by USDA-NIFA 2013-67015-21330.