Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities 英文参考文献.docVIP

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Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities 英文参考文献.doc

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Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities 英文参考文献

ReducedAPOBEC3HVariantAnti-ViralActivitiesAre AssociatedwithAlteredRNABindingActivities AnjieZhen1,JuanDu2,XiaohongZhou1,2,YongXiong3,Xiao-FangYu1,2* 1Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 2First AffiliatedHospital,JilinUniversity,Jilin,China,3DepartmentofMolecularBiophysicsandBiochemistry,YaleUniversity,NewHaven,Connecticut,UnitedStatesofAmerica Abstract APOBEC3H (A3H) is a member of the APOBEC3 family of proteins with varying activities against retroviruses and retrotransposons.TheA3Hgenecontainsseveralsinglenucleotidepolymorphismsanduptosevenhaplotypeshavebeen detected in humans. Although variations in anti-viral function among A3H haplotypes are not fully understood, only 15N105R-containingA3HvariantsareknowntohavepotentactivitiesagainstVif-deficientHIV-1.UniquemotifRLYY(F/Y)W ofAPOBEC3G(A3G)andAPOBEC3F(A3F)requiredfor7SLRNAbindingandHIV-1incorporationisalsoconservedinallA3H variants.LikeA3G,A3HHapIIalsodemonstratedhighbindingaffinitytohostsmallRNAssuchas7SLandYRNAs.Mutation ofacriticalaminoacid,W115Aresultedinreducedexpressionlevel,decreasedaffinityfor7SLRNA,impairmentofvirion packaging and reduced anti-viral activity. By comparison, A3H HapI had lower binding affinities to host small RNAs and reduced efficiency of virion incorporation, resulting in significantly reduced anti-viral activity. The SNP DN15 commonly foundinA3HHapIIIandHapIVabolishedtheirabilitiestoassociatewithRNAs,andA3HHapIID15Nfailedtopackageinto HIV-1 virions or exhibited any anti-viral activity. Finally, we showed that A3H variants had distinct cellular localization patterns, which correlated with their different RNA binding affinities. Thus, Pol-III RNA such as 7SL RNA binding is a conservedfeatureofpotentanti-HIVhumanAPOBEC3cytidinedeaminases. Citation:ZhenA,DuJ,ZhouX,XiongY,YuX-F(2012)ReducedAPOBEC3HVariantAnti-ViralActivitiesAreAssociatedwithAlteredRNABindingActivities.PLoS ONE