Mathematical Models of E-Antigen Mediated Immune Tolerance and Activation following Prenatal HBV Infection 英文参考文献.docVIP

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Mathematical Models of E-Antigen Mediated Immune Tolerance and Activation following Prenatal HBV Infection 英文参考文献.doc

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Mathematical Models of E-Antigen Mediated Immune Tolerance and Activation following Prenatal HBV Infection 英文参考文献

MathematicalModelsofE-AntigenMediatedImmune ToleranceandActivationfollowingPrenatalHBV Infection StancaM.Ciupe1*,SarahHews2 1DepartmentofMathematics,VirginiaTech,Blacksburg,Virginia,UnitedStatesofAmerica,2SchoolofNaturalSciences,HampshireCollege,Amherst,Massachusetts, UnitedStatesofAmerica Abstract WedevelopmathematicalmodelsfortheroleofhepatitisBe-antigenincreatingimmunologicaltoleranceduringhepatitis BvirusinfectionandproposemechanismsforhepatitisBe-antigenclearance,subsequentemergenceofapotentcellular immuneresponse,andtheeffectoftheseonliverdamage.Weinvestigatethedynamicsofvirus-immunecellsinteractions, andderiveparameterregimesthatallowforviralpersistence.Wemodifythemodeltoaccountformechanismsresponsible for hepatitis B e-antigen loss, such as seroconversion and virus mutations that lead to emergence of cellular immune response to the mutant virus. Our models demonstrate that either seroconversion or mutations can induce immune activation and that instantaneous loss of e-antigen by either mechanism is associated with least liver damage and is thereforemorebeneficialfordiseaseoutcomes. Citation: Ciupe SM, Hews S (2012) Mathematical Models of E-Antigen Mediated Immune Tolerance and Activation following Prenatal HBV Infection. PLoS ONE7(7):e39591.doi:10.1371/journal.pone.0039591 Editor:AndrewJ.Yates,AlbertEinsteinCollegeofMedicine,UnitedStatesofAmerica ReceivedJanuary27,2012;AcceptedMay24,2012;PublishedJuly2,2012 Copyright: ? 2012 Ciupe, Hews. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: SMC acknowledges support from National Science Foundation grant DMS-1022865. The funders had no role in study design, data collection and analysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:stanca@ Introduction lo