Herpes Simplex Virus Reorganizes the Cellular DNA Repair and Protein Quality Control Machinery 英文参考文献.docVIP

Pearls HerpesSimplexVirusReorganizestheCellularDNA RepairandProteinQualityControlMachinery SandraK.Weller* DepartmentofMolecular,MicrobialandStructuralBiology,TheUniversityofConnecticutHealthCenter,Farmington,Connecticut,UnitedStatesofAmerica When a virus infects a cell, it must contend with a hostile environmentandhostmachinerythatisintrinsicallyantiviral.One of the hallmarks of herpes simplex virus (HSV) infection is the dramaticreorganizationoftheinfectedcellnucleusleadingtothe formation of large globular replication compartments in which geneexpression,DNAreplication,andencapsidationoccur([1,2] and references therein) (see Figure 1). During infection, cellular factors that are beneficial to the virus are hijacked while other factors and pathways are degraded or inactivated. Two of the cellularhomeostaticpathwaysaffectedbyHSV-1infectionarethe protein quality control (PQC) and DNA damage response pathways.Theseeventsareorchestratedbyseveralviralproteins including the immediate early proteins ICP4, ICP27, ICP0, and ICP22thatallowthevirustocreateanenvironmentconduciveto infectionandcounteractthecell’sintrinsiccapacitytoinhibitviral infection[3–6].ICP4andICP27playessentialrolesinstimulation ofrobustviralgeneexpression[3,4].Theimmediateearlyprotein ICP0activatesviralandcellulargeneexpressionandfunctionsas anE3ubiquitinligasebydegradingseveralcellularproteins[5,7]. One target of ICP0 is PML, a major component of nuclear foci called ND10 that play a repressive role in viral gene expression. ICP0 interferes with several intrinsic host defense mechanisms including host interferon responses [5,7,8], thereby playing a major role in the establishment of a permissive viral infection. ICP22isrequiredforefficientgrowthandexpressionoflateviral genesinsomebutnotallculturedcells[6].ICP22alsoplaysarole in the post-translational modification of the cellular RNA polymerase II ([9] and references therein). As described below, theseimmediateearlyproteinsplayimportantrolesinremode