COX-2 Induction during Murine Gammaherpesvirus 68 Infection Leads to Enhancement of Viral Gene Expression

AUTOR(ES)

Symensma , Tonia L.

FONTE

American Society for Microbiology

RESUMO

The murine gammaherpesvirus 68 (MHV-68 or γHV-68) model provides many advantages for studying virus-host interactions involved in gammaherpesvirus replication, including the role of cellular responses to infection. We examined the effects of cellular cyclooxygenase-2 (COX-2) and its by-product prostaglandin E2 (PGE2) on MHV-68 gene expression and protein production following de novo infection of cultured cells. Western blot analyses revealed an induction of COX-2 protein in MHV-68-infected cells but not in cells infected with UV-irradiated MHV-68. Luciferase reporter assays demonstrated activation of the COX-2 promoter during MHV-68 replication. Two nonsteroidal anti-inflammatory drugs, a COX-2-specific inhibitor (NS-398) and a COX-1-COX-2 inhibitor (indomethacin), substantially reduced MHV-68 protein production in infected cells. Inhibition of viral protein expression and virion production by NS-398 was reversed in the presence of exogenous PGE2. Global gene expression analysis using an MHV-68 DNA array showed that PGE2 increased production of multiple viral gene products, and NS-398 inhibited production of many of the same genes. These studies suggest that COX-2 activity and PGE2 production may play significant roles during MHV-68 de novo infection.

Documentos Relacionados

• Kinetics of Murine Gammaherpesvirus 68 Gene Expression following Infection of Murine Cells in Culture and in Mice
• Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes
• Solubility enhancement of cox-2 inhibitors using various solvent systems
• Disruption of the Murine Gammaherpesvirus 68 M1 Open Reading Frame Leads to Enhanced Reactivation from Latency
• Transcription Program of Murine Gammaherpesvirus 68