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Endobiont Viruses Sensed by the Human Host – Beyond Conventional Antiparasitic Therapy 英文参考文献.docVIP

Endobiont Viruses Sensed by the Human Host – Beyond Conventional Antiparasitic Therapy 英文参考文献.doc

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Endobiont Viruses Sensed by the Human Host – Beyond Conventional Antiparasitic Therapy 英文参考文献

EndobiontVirusesSensedbytheHumanHost–Beyond ConventionalAntiparasiticTherapy RainaN.Fichorova1*,YujinLee1.,HidemiS.Yamamoto1.,YukoTakagi2,GaryR.Hayes3, RussellP.Goodman2¤a,XeniaChepa-Lotrea1¤b,OliviaR.Buck1,RyanMurray1¤c,TomaszKula2, DavidH.Beach4,BibhutiN.Singh3,MaxL.Nibert2 1Laboratory of Genital Tract Biology,Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School and Brigham and Women’s Hospital, Boston,Massachusetts,UnitedStatesofAmerica,2DepartmentofMicrobiologyandImmunobiology,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesof America, 3Department of Biochemistry and Molecular Biologyand Department ofObstetrics andGynecology, SUNY Upstate Medical University, Syracuse, New York, UnitedStatesofAmerica,4DepartmentofMicrobiologyandImmunology,SUNYUpstateMedicalUniversity,Syracuse,NewYork,UnitedStatesofAmerica Abstract Wide-spread protozoan parasites carry endosymbiotic dsRNA viruses with uncharted implications to the human host. Among them, Trichomonas vaginalis, a parasite adapted to the human genitourinary tract, infects globally ,250 million eachyearrenderingthemmoresusceptibletodevastatingpregnancycomplications(especiallypretermbirth),HIVinfection andHPV-relatedcancer.Whilefirst-lineantibiotictreatment(metronidazole)commonlykillstheprotozoanpathogen,itfails toimprovereproductiveoutcome.WeshowthatendosymbioticTrichomonasvirus,highlyprevalentinT.vaginalisclinical isolates,issensedbythehumanepithelialcellsviaToll-likereceptor3,triggeringInterferonRegulatingFactor-3,interferon type I and proinflammatory cascades previously implicated in preterm birth and HIV-1 susceptibility. Metronidazole treatmentamplifiedtheseproinflammatoryresponses.Thus,anewparadigmtargetingtheprotozoanvirusesalongwith theprotozoanhostmaypreventtrichomoniasis-attributableinflammatorysequelae. Citation:FichorovaRN,LeeY,YamamotoHS,TakagiY,HayesGR,etal.(2012)EndobiontVirusesSensedbytheHumanHost–BeyondConventionalAntiparasitic Therapy.PLoSONE7(11):e48418.doi:

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