The pathogenic Old World arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with a high rate of mortality in humans. Several LASV receptors ...SkiptomaincontentVirus-CellInteractionsLassaVirusCellEntryviaDystroglycanInvolvesanUnusualPathwayofMacropinocytosisJoelOppliger,GiuliaTorriani,AntonioHerrador,StefanKunzT.S.Dermody,EditorJoelOppligerFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteGiuliaTorrianiFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteAntonioHerradorFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteStefanKunzFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteT.S.DermodyUniversityofPittsburghSchoolofMedicineRoles:EditorFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteDOI: 10.1128/JVI.00257-16ArticleFigures&DataInfo&MetricsPDFABSTRACTThepathogenicOldWorldarenavirusLassavirus(LASV)causesaseverehemorrhagicfeverwithahighrateofmortalityinhumans.SeveralLASVreceptors,includingdystroglycan(DG),TAMreceptortyrosinekinases,andC-typelectins,havebeenidentified,suggestingcomplexreceptoruse.Uponreceptorbinding,LASVentersthehostcellviaanunknownclathrin-anddynamin-independentpathwaythatdeliversthevirustolateendosomes,wherefusionoccurs.HereweinvestigatedthemechanismsunderlyingLASVendocytosisinhumancellsinthecontextofproductivearenavirusinfection,usingrecombinantlymphocyticchoriomeningitisvirus(rLCMV)expressingtheLASVglycoprotein(rLCMV-LASVGP).WefoundthatrLCMV-LASVGPenteredhumanepithelialcellsviaDGusingamacropinocytosis-relatedpathwayindependentlyofalternativereceptors.Dystroglycan-mediatedentryofrLCMV-LASVGPrequiredsodiumhydrogenexchangers,actin,andtheGTPaseCdc42anditsdownstreamtargets,p21-activatingkinase-1(PAK1)andWiskott-Aldrichsyndromeprotein(N-Wasp).Unlikeothervirusesthatentercellsviamacropinocytosis,rLCMV-LASVGPentrydidnotinduceovertchangesincellularmorphologyandhardlyaffectedactindynamicsorfluiduptake