Stevenson, Natalie2013-10-142013-10-142013-05http://udspace.udel.edu/handle/19716/12685Gene regulation at the post-transcriptional level can be controlled by small segments of RNA called microRNAs (miRNAs). Previous studies have shown that Marek’s disease virus (MDV) has a variety of different miRNAs in its genome. A particularly important miRNA found in the virulent serotype 1 of MDV (MDV1) is MDV1-miR-M4. This miRNA has been shown to be necessary for the cancer caused by MDV and the level of its expression correlates with virulence of different MDV1 strains. Marek’s disease can be prevented by a vaccine based on a similar virus called herpesvirus of turkeys (HVT). Recombinant versions of HVT containing MDV1-miR-M4 proved to elevate viral loads in inoculated chickens compared to the parent HVT virus. This suggested that MDV1-miR-M4 may cause a reduction in immune function and enable more facile MDV infection to occur. We chose to investigate this hypothesis by studying Salmonella infections in chicks vaccinated with a HVT as well as with two different recombinant HVT vaccines: one based on MDV1-miR-M4 (rHVT-M4) and the second containing all of miRNAs proximal to MDV1-miR-M4 (rHVT-meqmiRs). Half of each group was treated with a commercial Salmonella vaccine and challenged with Salmonella Enteriditis (SE) after 1 week. Spleens harvested from the chickens were assayed for the presence of SE after 7 days. The chickens which were vaccinated with either rHVT-M4 or rHVT-meqmiRs proved to be more susceptible to the SE challenge than those vaccinated with the HVT parent. These studies suggest that one function of MDV1-miR-M4 is to cause the immunosuppression linked to MDV1 strains thereby contributing to MDV1 virulence.en-USThesis