Production of prostaglandin E 2 in response to infection with modified vaccinia Ankara virus

摘要

Prostaglandin E 2 (PGE 2) is an arachidonic acid (AA)-derived signaling molecule that can influence host immune responses to infection or vaccination. In this study, we investigated PGE 2 production in vitro by cells infected with the poxvirus vaccine strain, modified vaccinia Ankara virus (MVA). Human THP-1 cells, murine bone marrow-derived dendritic cells, and murine C3HA fibroblasts all accumulated PGE 2 to high levels in culture supernatants upon infection with MVA. We also demonstrated that MVA induced the release of AA from infected cells, and this was, most unusually, independent of host cytosolic phospholipase A 2 activity. The accumulation of AA and PGE 2 was dependent on viral gene expression, but independent of canonical NF-κB signaling via p65/RelA. The production of PGE 2 required host cyclooxygenase-2 (COX-2) activity, and COX-2 protein accumulated during MVA infection. The results of this study provide insight into a novel aspect of MVA biology that may affect the efficacy of MVA-based vaccines.