RNA Virus Replication Complexes 英文参考文献.docVIP

Pearls RNAVirusReplicationComplexes YizhiJaneTao*,QiaozhenYe DepartmentofBiochemistryandCellBiology,RiceUniversity,Houston,Texas,UnitedStatesofAmerica Themajorityofvirusesinfectinganimalsandplantstodayare RNAviruses[1].Therearedouble-stranded(ds)RNAviruseswith dsRNA genomes, as well as (+) and (2)RNA viruses whose genomesaresingle-stranded(ss)RNAofeitherpositiveornegative polarity. RNA viruses have small genomes that rarely exceed 30kb in size, and a large portion of their genomes is used to encode proteins involved in viral RNA replication. Viral RNA synthesisiscatalyzedbythevirallyencodedRNA-dependentRNA polymerase (RdRp), which lacks any proofreading activity. Although the details of RNA replication greatly vary among viruses,commonprinciplesclearlyexistintheorganizationofthe replicationmachineryofdifferentRNAviruses. (Figure1A).Thepalmdomaincontainsaninvariant,central,four- stranded b-sheet, with five highly conserved motifs named A to E. MotifsAandC,whichcontainthesequence–DxxxxD–and–GDD–, respectively, play important roles in metal ion coordination and nucleotidesubstrateselectionduringcatalysis.Thefingersandthumb domainsarelocatedonoppositesidesoftheactivesitecanyon.Most (+)RNA virus RdRps can initiate RNA synthesis de novo, but a numberofthemuseviralproteinprimers(VPgs)andproduceprotein- linkedgenomes.IntheRdRpfromthefoot-and-mouthdiseasevirus, uridylatedVPgoccupiesasitesimilartothetypicalRNAprimerinthe active site canyon, with the key residue Tyr3 and its associated uridylate(UMP)projectedintotheactivesite[7]. (+)RNAVirusesReplicateTheirGenomesonthe SurfaceofHostMembranes dsRNAVirusesReplicateandTranscribeTheir GenomesinIntactCoreParticles For many (+)RNA viruses, RNA replication requires viral enzymessuchasRdRp,helicase,cappingenzymes,andNTPase, aswellasnon-enzymaticproteinsthatparticipateintheassembly of the viral replication complex. Host cell proteins often play essential roles in (+)RNA virus replication as well. (+)RNA virus replicationisasymmetri