Endogenous MMTV Proviruses Induce Susceptibility to Both Viral and Bacterial Pathogens 英文参考文献.docVIP

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Endogenous MMTV Proviruses Induce Susceptibility to Both Viral and Bacterial Pathogens 英文参考文献.doc

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Endogenous MMTV Proviruses Induce Susceptibility to Both Viral and Bacterial Pathogens 英文参考文献

EndogenousMMTVProvirusesInduce SusceptibilitytoBothViralandBacterial Pathogens Sanchita Bhadra, Mary M.Lozano, Shelley M.Payne, Jaquelin P.Dudley* SectionofMolecularGeneticsandMicrobiologyandInstituteforCellularandMolecularBiology,UniversityofTexasatAustin,Austin,Texas,UnitedStatesofAmerica Most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (MMTV) (called Mtvs), whichhavemultiplereplicationdefects.ABALB/ccongenicmousestrainlackingallendogenousMtvs(Mtv-null)was resistanttoMMTVoralandintraperitonealinfectionandtumorigenesiscomparedtowild-typeBALB/cmice.Infection ofMtv-nullmicewithanMMTV-relatedretrovirus,typeBleukemogenicvirus,alsoresultedinseverelyreducedviral loads and failure to induce T-cell lymphomas, indicating that resistance is not dependent on expression of a superantigen(Sag)encodedbyexogenousMMTV.ResistancetoMMTVinMtv-nullanimalswasnotduetoneutralizing antibodies.Further,Mtv-nullmicewereresistanttorapidmortalityinducedbyintragastricinoculationoftheGram- negativebacterium,Vibriocholerae,butsusceptibilitytoSalmonellatyphimuriumwasnotsignificantlydifferentfrom BALB/c mice. Susceptibility to both MMTV and V. cholerae was reconstituted by the presence of any one of three endogenousMtvslocatedondifferentchromosomesandwasassociatedwithincreasedpathogenload.Oneofthese endogenousprovirusesisknowntoencodeonlySag.Therefore,Mtv-encodedSagappearstoprovideauniquegenetic susceptibilitytospecificvirusesandbacteria.SincehumanendogenousretrovirusesalsoencodeSags,thesestudies havebroadimplicationsforpathogen-inducedresponsesinmiceandhumans. Citation:BhadraS,LozanoMM,PayneSM,DudleyJP(2006)EndogenousMMTVprovirusesinducesusceptibilitytobothviralandbacterialpathogens.PLoSPathog2(12): e128.doi:10.1371/journal.ppat.0020128 Inthe?rstfewweeksoflife,milk-borneMMTVentersthe small intestine, where it penetrates M cells of the epithelial Introduction Pathogensarerecognizedbytheimmunesystem,whichhas been divided into innate and adaptive responses. In