RSV-induced prostaglandin E2 production occurs via cPLA2 activation: role in viral replication.

Prostaglandins (PGs) are lipid mediators that participate in the regulation of immunological and inflammatory responses, and PG production can affect viral replication. In this study, we have investigated the mechanism of PGE2 production in airway epithelial cells, following respiratory syncytial virus (RSV) infection, and its role in viral replication. We show that RSV infection strongly induces PGE2 secretion, in a time- and replication-dependent manner, through increased cyclooxygenase-2 (COX-2) expression, which occurs independently from viral or cellular protein synthesis. RSV infection induces arachidonic acid release through induction of cytoplasmic phospholipase A2 (cPLA2) enzymatic activity and its membrane translocation. Specific inhibitors of cPLA2 significantly block RSV-induced PGE2 secretion, indicating a key role of cPLA2 in viral-induced PG production. Blocking PG secretion, through cPLA2 or COX-2 inhibition, results in impairment of RSV replication and subsequent RSV-mediated epithelial cell responses, suggesting that inhibition of PG secretion could be beneficial in RSV infection by reducing proinflammatory mediator production.