GENERATION OF A CYTOMEGALOVIRUS EXPRESSING INTERLEUKIN-12 TO STUDY VIRAL DISSEMINATION AND IMMUNOGENICITY IN THE GUINEA PIG MODEL

Abstract

Congenital cytomegalovirus (CMV) is a leading cause of mental retardation and deafness in newborns; therefore, the development of a vaccine for the virus is of great importance. The guinea pig is the only small animal model for the study of congenital CMV infection and since HCMV and other CMV are highly specific to particular host species, guinea pig CMV (GPCMV) must be used for congenital CMV infection studies. Interleuking-12 (IL-12) is a proinflammatory cytokine dimer that stimulates T-cell activity during the immune response. The subunits of IL-12, especially the IL-12p40 (IL-12B) subunit, have potential for use as adjuvants in CMV vaccines to stimulate the T-cell response. The purpose of this project is to use molecular cloning strategies to create recombinant guinea pig CMV (GPCMV) strains expressing the guinea pig ortholog of IL-12B. This will allow the investigation of the effect of the IL-12B subunit on CMV pathogenicity in the guinea pig animal model as well as the impact of this cytokine on the resulting T-cell immune response to GPCMV infection.