Toreplicateinthehostcell,virusescommandeercellularsignalingpathways.Cytomegalovirus(CMV)isaDNAviruswiththatiswidespreadinthepopulationbutusuallycausesdiseaseonlyinimmunocompromisedindividualsandisalsoaviralcauseofbirthdefects.OneoftheactionsofCMVinthehostcellistostimulateMAPkinasepathways.Bothp38andERKkinasesareactivatedbyCMVinfectionthroughactivationmapkinasekinasesandinhibitionofphosphatases.OneresultofMapkinaseactivationbyCMVisactivationoftranscriptionofviralgenes,increasingtheproductionofviralgeneproducts.Bothp38andERKkinasescontributetotheactivationofviralgenesbycellulartranscriptionfactorsactingthroughtheviralUL4promoteratupstreamandbasaltranscriptionelements.Anothertargetofprolongedp38activationduringinfectionisRb,contributingtoviralreplication.ActivationofMKK1andMKK2leadstoErk1andErk2activation,andphosphorylationofdownstreamtargets.TheMEKK1kinaseregulatestheimmediateearlypromoterindirectlythroughdownstreamkinasesignalingandperhapsmoredirectlythroughactivationofNF-kB.MapkinasepathwaysactivatedbyCMVconvergeonincreasedtranscriptionofviralgenesandincreasedreplicationoftheviralgenome.BetterunderstandingofthemechanismsinvolvedintheinteractionofCMVwithcellularsignalingmachinerywillprovideimprovedwaystotreatCMV-mediateddisease.

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