Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis 英文参考文献.docVIP

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Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis 英文参考文献.doc

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Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis 英文参考文献

AmeobalPathogenMimivirusInfectsMacrophages throughPhagocytosis EricGhigo1,Ju¨rgenKartenbeck2,3,PhamLien1,LucasPelkmans4,ChristianCapo1,Jean-LouisMege1, DidierRaoult1* 1URMITE CNRS UMR 6236 - IRD 3R198, Universite′ de la Me′diterrane′e, Marseille, France, 2Abteilung fu¨r Zellbiologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg,Germany,3InstituteofAppliedPhysics,ETHZu¨rich,Zu¨rich,Switzerland,4InstituteforMolecularSystemsBiology,ETHZu¨rich,Zu¨rich,Switzerland Abstract Mimivirus,orAcanthamoebapolyphagamimivirus(APMV),agiantdouble-strandedDNAvirusthatgrowsinamoeba,was identifiedforthefirsttimein2003.Entrybyphagocytosiswithinamoebahasbeensuggestedbutnotdemonstrated.We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive APMV replication. Clathrin- and caveolin-mediated endocytosis pathways, as well as degradative endosome-mediated endocytosis,werenotusedbyAPMVtoinvademacrophages.Ultrastructuralanalysisshowedthatprotrusionswereformed aroundtheenteringvirus,suggestingthatmacropinocytosisorphagocytosiswasinvolvedinAPMVentry.Reorganizationof the actin cytoskeleton and activation of phosphatidylinositol 3-kinases were required for APMV entry. Blocking macropinocytosisandthelackofAPMVcolocalizationwithrabankyrin-5showedthatmacropinocytosiswasnotinvolved inviralentry.Overexpressionofadominant-negativeformofdynamin-II,aregulatorofphagocytosis,inhibitedAPMVentry. Altogether,ourdatademonstratedthatAPMVentersmacrophagesthroughphagocytosis,anewpathwayforvirusentryin cells.Thisreinforcestheparadigmthatintra-amoebalpathogenshavethepotentialtoinfectmacrophages. Citation: Ghigo E, Kartenbeck J, Lien P, Pelkmans L, Capo C, et al. (2008) Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis. PLoS Pathog4(6):e1000087.doi:10.1371/journal.ppat.1000087 Editor:MichaelFarzan,HarvardMedicalSchool,UnitedStatesofAmerica ReceivedDecember17,2007;AcceptedMay9,2008;PublishedJune13,2008 Copyright: ? 2008 Ghigo et a