Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees 英文参考文献.docVIP

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Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees 英文参考文献.doc

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Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees 英文参考文献

EvaluationofIL-28BPolymorphismsandSerumIP-10in HepatitisCInfectedChimpanzees BabsE.Verstrepen1.,NatasjaG.deGroot2.,ZwierM.A.Groothuismink3,ErnstJ.Verschoor1,RikA.de Groen3,WillyM.Bogers1,HarryL.A.Janssen3,PetraMooij1,RonaldE.Bontrop2,GerritKoopman1, AndreBoonstra3* 1DepartmentofVirology,BiomedicalPrimateResearchCentre,Rijswijk,TheNetherlands,2DepartmentofComparativeGeneticsandRefinement,BiomedicalPrimate ResearchCentre,Rijswijk,TheNetherlands,3DepartmentofGastroenterologyandHepatology,ErasmusMCUniversityHospital,Rotterdam,TheNetherlands Abstract Inhumans,clearanceofhepatitisCvirus(HCV)infectionisassociatedwithgeneticvariationneartheIL-28Bgeneandthe induction of interferon-stimulated genes, like IP-10. Also in chimpanzees spontaneous clearance of HCV is observed. To studywhethersimilarcorrelationsexistintheseanimals,adirectcomparisonofIP-10andIL-28Bpolymorphismbetween chimpanzeesandpatientswasperformed.AllchimpanzeesstudiedweremonomorphicforthehumanIL-28BSNPswhich areassociatedwithspontaneousandtreatmentinducedHCVclearanceinhumans.Asaresult,theseparticularSNPscannot be used for clinical association studies in chimpanzees. Although these human SNPs were absent in chimpanzees, gene variation in this region was present however, no correlation was observed between different SNP-genotypes and HCV outcome.Strikingly,IP-10levelsinchimpanzeescorrelatedwithHCV-RNAloadandcGT,whilesuchcorrelationswerenot observedinhumans.ThecorrelationbetweenIP-10,cGTandvirusloadinchimpanzeeswasnotfoundinpatientsandmay be due to the lack of lifestyle-related confounding factors in chimpanzees. Direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients in relation to HCV infection, illustrates that the IFN-pathways are importantduringHCVinfectioninbothspecies.TheGenbankEMBLaccessionnumbersassignedtochimpanzeesspecific sequencesneartheIL-28BgeneareHE599784andHE599785. Citation: Verstrepen BE, deGrootNG,Groothuismink ZMA,VerschoorEJ,de Groen RA,etal.(2012)Evaluation o