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An Avirulent Mutant of Rabies Virus Is Unable To Infect.pdf

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JOURNALOFVIROLOGYJan.1998p.273–278Vol.72No.10022-538X/98/$04.00ϩ0Copyright©1998AmericanSocietyforMicrobiologyAnAvirulentMutantofRabiesVirusIsUnableToInfectMotoneuronsInVivoandInVitroPATRICECOULON12JEAN-PIERRETERNAUX2ANNEFLAMAND11ANDCHRISTINETUFFEREAU*LaboratoiredeGe´ne´tiquedesVirusCentreNationaldelaRechercheScientifique91198GifsurYvetteCedex1andUnite´deNeurocyberne´tiqueCellulaireCentreNationaldelaRechercheScientifique13009Marseille2FranceReceived21July1997/Accepted23September1997Anantigenicdoublemutantofrabiesvirus(challengevirusstandard[CVS]strain)wasselectedbysucces-siveuseoftwoneutralizingantiglycoproteinmonoclonalantibodiesbothspecificforantigenicsiteIII.Thismutantdifferedfromtheoriginalvirusstrainbytwoaminoacidsubstitutionsintheectodomainoftheglyco-protein.Thelysineinposition330andthearginineinposition333werereplacedbyasparagineandmethi-oninerespectively.Thisdoublemutantwasnotpathogenicforadultmice.Wheninjectedintramuscularlyintotheforelimbsofadultmicethisviruscouldnotpenetratethenervoussystemeitherbythemotororbythesensoryroutewhilerespectivesinglemutantsinfectedmotoneuronsinthespinalcordandsensoryneuronsinthedorsalrootganglia.InvitroexperimentsshowedthatthedoublemutantwasabletoinfectBHKcellsneuroblastomacellsandfreshlypreparedembryonicmotoneuronsalbeitwithalowerefficiencythantheCVSstrain.