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

[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...

[学科分类] 生理学

[关键词] restriction factors;HIV‐1;HLA class I