Increased expression of intrinsic antiviral genes in HLA‐B*57‐positive individuals

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: restriction factors;    HIV‐;    1;    HLA class I;   

DOI  :  10.1189/jlb.0313150

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThegeneticbackgroundofHIV‐1‐infectedsubjects,particularlytheHLAclassIhaplotype,appearstobecriticalindeterminingdiseaseprogressionrates,thoughttobearesultoftheroleofHIV‐1‐specificCD8+Tcellresponses.TheHLA‐B*57alleleisstronglyassociatedwithviremicsuppressionandslowerdiseaseprogression.However,thereisconsiderableheterogeneityinHIV‐1diseaseprogressionratesamongHLA‐B*57‐positivesubjects,suggestingthatadditionalfactorsmayhelptocontainviralreplication.Inthisreport,weinvestigatedtheassociationbetweenhostrestrictionfactors,otherestablishedimmunologicalparameters,andHLAtypeinHIV‐1‐seronegativeindividuals.Ourresultsdemonstratethathealthy,uninfectedHLA‐B*57‐positiveindividualsexhibitsignificantlyhighergene‐expressionlevelsofhostrestrictionfactors,suchasAPOBEC3A,APOBEC3B,BST‐2/tetherin,andISG15.Interestingly,HLA‐B*57individualshavesignificantlylowerCD4+TcellfrequenciesbutharborslightlymoreactivatedCD4+TcellscomparedwiththeirHLA‐B*35counterparts.WedetectedsignificantcorrelationsbetweenCD4+TcellactivationandexpressionofseveralAPOBEC3familymembers,BST‐2/tetherin,SAMHD1,andTRIM5αinHLA‐B*57‐positiveindividuals.Toourknowledge,thisisthefirstreportshowingdistinctassociationsbetweenhostrestrictionfactorsandHLAclassIgenotype.OurresultsprovideinsightsintonaturalprotectionmechanismsandimmunityagainstHIV‐1thatfalloutsideofclassicalHLA‐mediatedeffects...

【 授权许可】

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