Recombinant murine cytomegalovirus vector activates human monocyte-derived dendritic cells in a NF-kappaB dependent...

To evaluate the potential use of recombinant murine cytomegalovirus (MCMV) as an antigen delivery vector, we examined the cytokine and CD80 and CD86 expression profiles of MCMV encoding either enhanced green fluorescent protein gene (MCMV-EGFP) or human immunodeficiency virus-1 glycoprotein gp120 gene (MCMV-gp120) infected monocyte-derived dendritic cells (Mo-DC) and investigated the role of nuclear factor kappa B (NF-kappaB) in Mo-DC activation. Results showed that MCMV triggered the induction of inflammatory cytokines and/or CD80 and CD86 up-regulation in Mo-DC. UV-inactivated MCMV exhibited a reduced production of inflammatory cytokines and a lowered expression of CD80 and CD86 compared with live MCMV infection. Treatment of cells with a NF-kappaB peptide inhibitor prior to MCMV infection reduced the induction of cytokines and CD80 and CD86 up-regulation. Overall, the results suggest that recombinant MCMV vectors activate human Mo-DC in a NF-kappaB dependent pathway. The abortive infection or de novo gene expression greatly enhances the activation of Mo-DC by MCMV vectors.