| Viruses and other pathogens have evolved elegant mechanisms to evade, control, and otherwise abrogate the host immune system. They have been found to alter host cell-surface markers, encapsulate to avoid detection, and even integrate directly into the host genome. Viruses provide a unique opportunity to study pathogen-host genetic interactions and one example is Marek's disease virus (MDV). MDV is an oncogenic herpes virus that causes Marek's disease (MD) in chickens and as a result of enormous agricultural economic losses worldwide, has been extensively studied over the past 40 years. The virus is currently controlled in chickens through the use of vaccines. Unfortunately the vaccines have a limited lifespan of approximately 10 years, at which point new strains with increased virulence appear. MDV is a valuable model as it can be studied both in vitro and in vivo in its natural host system. Despite the volume of research and attention given to MDV, the exact mechanisms of virus integration, host-virus genome interactions, and cellular persistence remain unknown.;The research described within this dissertation investigated whether integration is part of the natural lifecycle of the virus by addressing key questions of involved cell type, timing, and virus-strain using molecular cytogenetics wherein single cells were examined. The results show that integration is a key feature of the viral lifecycle and is associated with both B and T lymphocytes during the early lytic, latent, and transformed periods. The data suggest association of integration with latency but that integration alone is not sufficient for transformation. Overall the study provides new insights into the nature of virus and host genome interactions and the role of integration as relates to pathogenesis and transformation. |
