Entry Tropism of BK and Merkel Cell Polyomaviruses in Cell Culture 英文参考文献.docVIP

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Entry Tropism of BK and Merkel Cell Polyomaviruses in Cell Culture 英文参考文献.doc

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Entry Tropism of BK and Merkel Cell Polyomaviruses in Cell Culture 英文参考文献

EntryTropismofBKandMerkelCellPolyomavirusesin CellCulture RachelM.Schowalter1,WilliamC.Reinhold2,ChristopherB.Buck1* 1Tumor Virus Molecular Biology Section, Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, United States of America, 2Laboratory of MolecularPharmacology,CenterforCancerResearch,NationalCancerInstitute,Bethesda,Maryland,UnitedStatesofAmerica Abstract MerkelCellPolyomavirus(MCVorMCPyV)wasrecentlydiscoveredinanaggressiveformofskincancerknownasMerkelcell carcinoma(MCC).IntegrationofMCVDNAintothehostgenomelikelycontributestothedevelopmentofMCCinhumans. MCVinfectioniscommonandmanyhealthypeopleshedMCVvirionsfromthesurfaceoftheirskin.MCVDNAhasalsobeen detectedinsamplesfromavarietyofothertissues.AlthoughMCCtumorsserveasarecordthatMCVcaninfecttheMerkel celllineage,thetruetissuetropismandnaturalreservoirsofMCVinfectioninthehostarenotknown.Inanefforttogain insightintothetissuetropismofMCV,andtopossiblyidentifycellularfactorsresponsibleformediatinginfectiousentryof thevirus,theinfectionpotentialofhumancellsderivedfromavarietyoftissueswasevaluated.MCVgenetransfervectors (pseudoviruses)carryingreporterplasmidDNAencodingGFPorluciferasegeneswereusedtotransducekeratinocytesand melanocytes,aswellaslinesderivedfromMCCtumorsandtheNCI-60panelofhumantumorcelllines.MCVtransduction was compared to transduction with pseudoviruses based on the better-studied human BK polyomavirus (BKV). The efficiencyofMCVandBKVtransductionofvariouscelltypesoccasionallyoverlapped,butoftendifferedgreatly,andnoclear tissuetypepreferenceemerged.ApplicationofnativeMCVvirionstoasubsetofhighlytransduciblecelltypessuggested thatthelinesdonotsupportrobustreplicationofMCV,consistentwithrecentproposalsthattheMCVlatephasemaybe governedbycellulardifferentiationinvivo.TheavailabilityofcarefullycuratedgeneexpressiondatafortheNCI-60panel shouldmaketheMCVandBKVtransductiondatafortheselinesausefulreferenceforfuturestudiesaimedatelucidationof theinfectiousentrypathwaysofthesevirus