VIRUSVERSUSBODY

VIRUSVERSUSBODY: THEEFFECTOFTHEHEPATITISCVIRUSNS5APROTEIN ONTHEANTIVIRALRESPONSEANDCANCERDEVELOPMENT by MOLLIJONESCRENSHAW BachelorofScience,2005 TexasA&MUniversity CollegeStation,Texas SubmittedtotheGraduateFacultyofthe CollegeofScienceandEngineering TexasChristianUniversity inpartialfulfillmentoftherequirements forthedegreeof MasterofScience December2009

ACKNOWLEDGEMENTS Iwouldliketoexpressmygratitudetoeachofmyinstructorsandpeersfortheir encouragementandsupportoverthepasttwoyears.Theyhaveimpactedmenotonly asastudent,butalsoasafriend. ToDr.GiridharAkkaraju,whoissomuchmorethanjustagraduateadvisor.Hispassion forteachingcombinedwithhisunendingpatiencehavemadehimbothmymentorand myrole‐model.Hehasinspiredmyloveofscience,andincreasedmydesiretolearn witheachstepofthisjourney.Icanonlyhopetoimpactmyfuturestudentsintheway thathehasimpactedme. TomyFather,Dr.JesseJones,thefirsttoopenmyeyestothewondersofscience.His loveofmedicineandnaturewasevidenttomeevenatayoungage,andhiswillingness toanswerallmyquestionsfueledafireforlearningthatIhopetopassontomy childrenoneday. TomyMother,Mrs.HolliJones,whosewisdomandencouragementhavemadeeven themostdifficultdaysbetter.Phoneconversationswithherareoftenahighlightofmy day,andIlookforwardtothemanygoodtalkswehavelyingaheadofus. Tomyhusband,Ben.Despitethemanylatehoursandweekendsfilledwithlabwork, hasneverbeenanythingbutloving.Heencouragesmeworkhardandtochasemy dreams,andcanturnmytearstolaughterwhenI'mfeelingoverwhelmed.Youhaveall myloveandsupport,always. ii iii
TABLEOFCONTENTS Acknowledgements………………………………………………………………………………………………………..ii ListofFigures…………………………………………………………………………………………………………………iv Introduction……………………………………………………………………………………………………………………1 I.InfectivityandTreatment…………………………………………………………………………………1 II.HepatitisCVirusLifeCycle………………………………………………………………………….....3 III.TheNS5AProtein…………………………………………………………………………………………..6 IV.MechanismsoftheHostCellAntiviralResponse……………………………………….....7 V.NS5ARepressestheAntiviralReponses………………………………………………..……….9 VI.HepatitisCVirusCausesHepatocellularCarcinoma………………………………….….10 VII.TheHostCellCycle……………………………………………………………………………………..11 VIII.MechanismsofApoptosis………………………………………………………………………….11 IX.MechanismsofGrowthandProliferation…………………………………………………….14 X.MechanismsbywhichHepatitisCVirusCausesHepatocellularCarcinoma.....15

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