Distinct Determinants in HIV-1 Vif and Human APOBEC3 Proteins Are Required for the Suppression of Diverse Host Anti-Viral Proteins 英文参考文献.docVIP

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Distinct Determinants in HIV-1 Vif and Human APOBEC3 Proteins Are Required for the Suppression of Diverse Host Anti-Viral Proteins 英文参考文献.doc

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Distinct Determinants in HIV-1 Vif and Human APOBEC3 Proteins Are Required for the Suppression of Diverse Host Anti-Viral Proteins 英文参考文献

DistinctDeterminantsinHIV-1VifandHumanAPOBEC3 ProteinsAreRequiredfortheSuppressionofDiverse HostAnti-ViralProteins WenyanZhang1,3,GongyingChen1,4,AnnaMariaNiewiadomska1,RongzhenXu2,Xiao-FangYu1,2* 1DepartmentofMolecularMicrobiologyandImmunology,JohnsHopkinsBloombergSchoolofPublicHealth,Baltimore,Maryland,UnitedStatesofAmerica,2Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China, 3College of Life Science, Jilin University, Jilin, China, 4The Sixth Hospital of Hangzhou, Zhejiang,China Abstract Background:APOBEC3G(A3G)andrelatedcytidinedeaminasesoftheAPOBEC3familyofproteinsarepotentinhibitorsof manyretroviruses,includingHIV-1.FormationofinfectiousHIV-1requiresthesuppressionofmultiplecytidinedeaminases byVif.HIV-1VifsuppressesvariousAPOBEC3proteinsthroughthecommonmechanismofrecruitingtheCullin5-ElonginB- ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized. MethodsandFindings:Inthepresentstudy,wehavedemonstratedthattheregionsofAPOBEC3F(A3F)thatarerequired for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD) of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation.WealsoobservedthatthedomainsofHIV-1Vifthatareuniquelyrequiredforitsfunctionalinteractionwith full-lengthA3FarealsorequiredforthedegradationoftheC-CDDofA3F;incontrast,thoseVifdomainsthatareuniquely requiredforfunctionalinteractionwithA3GarenotrequiredforthedegradationoftheC-CDDofA3F.Interestingly,theHIV- 1VifdomainsrequiredforthedegradationofA3FarealsorequiredforthedegradationofA3CandA3DE.Ontheother hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminasesA3CandA3DE. Conclusions:Ourdatasugges