Antibody protects against lethal infection with the neurally spreading reovirus type 3 (Dearing).

Themammalian reoviruses haveprovided avaluable modelforstudying thepathogenesis ofviral infections ofthecentral nervoussystem(CNS). We haveusedthismodeltostudy theeffect ofantibody on disease produced bytheneurally spreading reovirus type3(Dearing) (T3). Polyclonal andmonoclonal antibodies protect micefromfatal infection withT3after either footpad or intracerebral viruschallenge. Protection occurswithmonoclonal antibodies directed against theviralcellattachment protein sigma1,andwith polyclonal antisera without T3sigma1binding activity. Invivoprotection occurswithbothneutralizing and nonneutralizing monoclonal antibodies. Antibody-mediated protection doesnotrequire serum complement and,underspecific circumstances, canoccurviaFc-independent mechanisms. Antibody canprotect micewhen transferred up to5daysafter intracerebral challenge andupto7daysafter footpad challenge, timeswhenhigh titers ofvirus arepresent intheCNS.Thus, antibody mediated protection against thisneurally spreading virus doesnotrequire neutralizing antibody or serum complement andoccurseveninthefaceofestablished CNS infection. Infection ofneonatal micewithmammalian reoviruses has provided a useful modelforstudying viral pathogenesis. Someofthefunctions oftheproteins encoded byindividual viral genesatspecific stagesinreovirus pathogenesis have beenidentified (56, 61). Forexample, following footpad (FP) inoculation withreovirus type3Dearing (hereafter designatedT3),virusreplicates inskeletal muscleandthen spreads vianervestothecentral nervoussystem(CNS)(63; K. L.TylerandB. N. Fields, unpublished data). The capacity ofT3tospread vianervesisdetermined bytheviral Sidouble-stranded RNA segmentandoccursviathemicrotubule-associated