Efficacy and immunological mechanisms of type 1 interferon gene therapy in murine cytomegalovirus

摘要: This thesis presents a comparative analysis of the type I Interferon (IFN) subtypes and an evaluation their potential as DNA vaccines in model murine cytomegalovirus (MCMV) infection disease. MCMV induces acute chronic phases myocarditis, heart disease characterised by inflammatory cell infiltrate, susceptible BALB/c mice. The IFNs comprise 14 IFN alpha genes human >10 mouse with single beta gene both species, however, purpose multiplicity has remained unclear to date. An extensive panel subtype genes, including IFNA1, A2, A4, A5, A6, A9 B, were sub-cloned into mammalian expression vector pkCMVint (Vical, Inc.) for mice. These constructs express biologically active vitro vivo systemic, low level persisting up 4 weeks. The individual differentially affect immune response challenge. IFNA6 proved most efficacious, reducing viral replication inflammation phase Data suggests this occurs via induction Th1-like cytokine antibody response. Furthermore, inoculation after was shown protect mice from onset myocarditis. Characterisation IFN-treated, MCMV-infected demonstrated that modulate cells infiltrating myocardium during Notably, reduced CD8+ CD4+ T B numbers associated Finally, coadministration IFNs, particular, IFNB, synergistically improved immunotherapy against The findings detailed here highlight importantly, demonstrate have differential antiviral immunomodulatory efficacies