Immune control and failure in HCV infection—tipping the balance

[摘要] Despitethedevelopmentofpotentantiviraldrugs,HCVremainsaglobalhealthproblem;globaleradicationisalongwayoff.Inthisreview,wediscusstheimmuneresponsetoHCVinfectionandparticularly,theinterplaybetweenviralstrategiesthatdelaytheonsetofantiviralresponsesandhoststrategiesthatlimitoreveneradicateinfectedcellsbutalsocontributetopathogenesis.AlthoughHCVcandisablesomecellularvirus‐sensingmachinery,IFN‐stimulatedantiviralgenesareinducedintheinfectedliver.WhereasepitopeevolutioncontributestoescapefromTcell‐mediatedimmunity,chronichighantigenloadmayalsoblunttheTcellresponsebyactivatingexhaustionortolerancemechanisms.TheevasivemaneuversofHCVlimitsterilizinghumoralimmunitythroughrapidevolutionofdecoyepitopes,epitopemasking,stimulationofinterferingantibodies,lipidshielding,andcell‐to‐cellspread.WhereasthemajorityofHCVinfectionsprogresstochronichepatitiswithpersistentviremia,atleast20%ofpatientsspontaneouslycleartheinfection.Mostoftheseareprotectedfromreinfection,suggestingthatprotectiveimmunitytoHCVexistsandthataprophylacticvaccinemaybeanachievablegoal.Itisthereforeimportantthatweunderstandthecorrelatesofprotectiveimmunityandmechanismsofviralpersistence...

[学科分类] 生理学

[关键词] immune evasion;innate immunity;interferons;T lymphocytes;B lymphocytes;NK cells