engleski

''Genetic manipulation of viral genome as a tool to generate more efficient virus vaccine and vaccine vectors''

NKG2D is a potent activating receptor expressed by cells of innate and adaptive immunity that recognizes cell surface molecules structurally related to MHC-I proteins induced by infection or other type of cellular stress. Engagement of NKG2D leads to cytotoxicity and cytokine secretion by NK cells, or to costimulation of CD8+ T cells. Both human cytomegalovirus (CMV) and mouse CMV deployed evasive mechanisms to prevent expression of NKG2D ligands. So far we have characterized four mouse CMV proteins involved in the down-modulation of NKG2D ligands in infected cells. Deletion of any of these viral immunoevasive genes involved in regulation of NKG2D ligands resulted in virus attenuation in vivo. Based on the attenuation of viruses lacking NKG2D immunoevasins we proposed that the insertion of genes encoding NKG2D ligands in place of genes encoding their viral inhibitors, could be an appropriate approach for immunological attenuation of live vaccine. We have recently shown that despite the strong NK cell-mediated attenuation, mouse CMV engineered to express NKG2D ligand RAE-1gamma elicits a strong and long-lasting antiviral CD8 response, providing protection against lethal virus challenge (Slavuljica et al, JCI 2010). In this talk I will overview the current knowledge on CMV downregulation of NKG2D signaling and our recent results using CMV expressing NKG2D ligand as a live attenuated vaccine and vaccine vector.

NKG2D; cytomegalovirus; immune evasion; CMV proteins

nije evidentirano