Prostaglandin E2 Induction during Mouse Adenovirus Type 1 Respiratory Infection Regulates Inflammatory Mediator Generation but Does Not Affect Viral Pathogenesis

Respiratory viruses cause substantial disease and are a significant healthcare burden. Virus-induced inflammation can be detrimental to the host, causing symptoms during acute infection and leading to damage that contributes to long-term residual lung disease. Prostaglandin E-2 (PGE(2)) is a lipid mediator that is increased in response to many viral infections, and inhibition of PGE(2) production during respiratory viral infection often leads to a decreased inflammatory response. We tested the hypothesis that PGE(2) promotes inflammatory responses to mouse adenovirus type 1 (MAV-1) respiratory infection. Acute MAV-1 infection increased COX-2 expression and PGE(2) production in wild type mice. Deficiency of the E prostanoid 2 receptor had no apparent effect on MAV-1 pathogenesis. Virus-induced induction of PGE(2), IFN-gamma, CXCL1, and CCL5 was reduced in mice deficient in microsomal PGE synthase-1 (mPGES-1(-/-) mice). However, there were no differences between mPGES-1(+/+) and mPGES-1(-/-) mice in viral replication, recruitment of leukocytes to airways or lung inflammation. Infection of both mPGES-1(+/+) and mPGES-1(-/-) mice led to protection against reinfection. Thus, while PGE(2) promotes the expression of a variety of cytokines in response to acute MAV-1 infection, PGE(2) synthesis does not appear to be essential for generating pulmonary immunity.