LASSA VIRUS SHOWS COMPLEX RECEPTOR USE. The first LASV receptor was identified as dystroglycan (DG), a ubiquitously expressed conserved cellular ...SkiptomaincontentGemLassaVirusCellEntryRevealsNewAspectsofVirus-HostCellInteractionGiuliaTorriani,ClaraGalan-Navarro,StefanKunzBillyTsai,EditorGiuliaTorrianiFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteClaraGalan-NavarroFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteStefanKunzFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteBillyTsaiUniversityofMichiganMedicalSchoolRoles:EditorFindthisauthoronGoogleScholarFindthisauthoronPubMedSearchforthisauthoronthissiteDOI: 10.1128/JVI.01902-16ArticleFigures&DataInfo&MetricsPDFABSTRACTViralentryrepresentsthefirststepofeveryviralinfectionandisadeterminantforthehostrangeanddiseasepotentialofavirus.Here,wereviewthelatestdevelopmentsoncellentryofthehighlypathogenicOldWorldarenavirusLassavirus,providingnovelinsightsintothecomplexvirus-hostcellinteractionofthisimportanthumanpathogen.Wewillcovernewdiscoveriesonthemolecularmechanismsofreceptorrecognition,endocytosis,andtheuseoflateendosomalentryfactors.INTRODUCTIONAmongthearenaviruses,Lassavirus(LASV)representsthemostprevalenthumanpathogen,withseveralhundredthousandinfectionsperyear(1).CarriedbypersistentinfectionofthereservoirrodenthostMastomysnatalensis,LASVisendemicinlargepartsofwesternAfrica.Arenavirusesareenvelopednegative-strandRNAviruseswithanonlyticlifecycleconfinedtothecytosol.Thearenavirusgenomecomprisesasmall(S)RNAsegmentencodingtheenvelopeglycoproteinprecursor(GPC)andthenucleoprotein(NP)andanLsegmentcodingforthematrixprotein(Z)aswellastheviralpolymerase(L)(2).TheGPCissynthesizedasasinglepolypeptideandundergoesprocessing,yieldingastablesignalpeptide(SSP),N-terminalGP1,andtransmembraneGP2.GP1bindstocellularreceptors,whereasGP2mediatesviralfusionandstructurallyresemblesclassIviralfusionproteins.Uponreceptorbinding,LASVentersthehostcellv