COX-2 induction during murine gammaherpesvirus 68 infection leads to enhancement of viral gene expression.
The murine gammaherpesvirus 68 (MHV-68 or gammaHV-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 E(2) (PGE(2)) 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 PGE(2). Global gene expression analysis using an MHV-68 DNA array showed that PGE(2) 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 PGE(2) production may play significant roles during MHV-68 de novo infection.
Symensma
Tonia L
TL
Department of Molecular and Medical Pharmacology, the UCLA AIDS Institute, University of California at Los Angeles, Los Angeles, California 90095, USA.
Martinez-Guzman
DeeAnn
D
Jia
Qingmei
Q
Bortz
Eric
E
Wu
Ting-Ting
TT
Rudra-Ganguly
Nandini
N
Cole
Steve
S
Herschman
Harvey
H
Sun
Ren
R
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000502:physiology; D004790:Enzyme Induction; D018142:Gammaherpesvirinae / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D009578:Nitrobenzenes / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D013449:Sulfonamides / Q000494:pharmacology
D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin