Lack of Effect of Murine Norovirus Infection on a Mouse Model of Bacteria-Induced Colon Cancer

摘要

Murinenorovirus(MNV)isendemicinmouseresearchfacilitiesintheUnitedStatesandEurope,withaprevalenceashighas58%to64%.BecauseofMNV'sorofecalrouteofinfection,clinicallysilentpersistentinfectionsinsomemousestrains,andproclivityformacrophageanddendriticcells,itspresenceinmousecolonieshaspotentialtoalterphenotypesinexperimentalmousemodels,particularlythoseinvolvinginflammationandimmunologicresponses.AlthoughMNVissubclinical,notcausingovertdiseaseinimmunocompetentmice,wefoundthatMNVinfectioncanacceleratebacteria#8211;inducedinflammatoryboweldisease(IBD)progressioninMdr1asup#8211;/#8211;/supmice.ThestudiespresentedhereexaminedwhetherMNVinfectionalsoaffectsthephenotypeofabacteriallydrivenmousemodelofinflammation#8211;associatedcoloncanceringeneticallysusceptibleSmad3sup#8211;/#8211;/supmice.Invitrocultureofbone#8211;marrow#8212;derivedmacrophages(BMDM)wasusedtodeterminewhetherMNV4influencedmacrophagecytokineproduction.Forinvivostudies,Smad3sup#8211;/#8211;/supmicewereinfectedwithMNV4oneweekpriortoinfectionwithHelicobacter.Miceweremonitoredfor17to32wkfordevelopmentofIBDandcoloncancer,andtissueswereanalyzedhistopathologically.AlthoughinvitroinfectionofBMDMwithMNV4ledtoincreasedinflammatorycytokineproduction,infectionwithMNV4invivodidnotresultinanystatisticallysignificantdifferencesinsurvival,IBDscores,tumorincidence,ortumorphenotypeinSmad3sup#8211;/#8211;/supmice.Inaddition,MNVinfectionalonedidnotresultinIBDorcoloncancer.ThereforeMNVinfectionaloneorinconjunctionwithHelicobacterdoesnotalterthedevelopmentorprogressionofIBDorcoloncancerinSmad3sup#8211;/#8211;/supmice.