[Truncated abstract] Cytomegalovirus (CMV) is a member of the herpesviridae family, and is commonly latent in healthy individuals. Infection or reactivation of the virus can cause severe disease in individuals with a weakened immune system, including newborns, transplant patients and acquired Immune deficiency syndrome patients. A successful vaccine for CMV is yet to be discovered, but it remains of the highest priority. A better understanding of the immune responses to the virus, and how the virus subverts these responses, is required for the design of more effective immunotherapies. Although CMVs are highly species-specific, replication characteristics, gene organisation and expression, the function of viral proteins, morphology, pathogenesis (both in vitro and in vivo), and disease symptoms, are similar in both mice and humans. Infection with the murine form of CMV, murine CMV (MCMV), has proved an important model for studying how the virus is dealt with in vivo. The first chapter of this thesis reviews the current understanding of the innate and adaptive immune responses to MCMV infection. It discusses the mechanisms used by the virus to evade these host responses, and the immunotherapies currently being explored for the treatment and prevention of CMV infection and/or disease. This review further focuses on how CMV affects antigen presenting cells such as dendritic cells (DCs), and how DCs may be manipulated therapeutically to enhance downstream responses to the virus. Chapter 2 investigates the function of a viral cytokine homologue in relation to its effects on murine DCs. These studies specifically focused on the CMV homologue of IL-10, a host cytokine involved in dampening the immune response following an infection to prevent immunopathology. The studies presented in this chapter demonstrate the strict species-specificity of the CMV viral IL-10 homologues therefore making it impossible to investigate the function of this CMV protein in vivo.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2010|