Rev Proteins of Human and Simian Immunodeficiency Virus Enhance RNA Encapsidation 英文参考文献.docVIP

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Rev Proteins of Human and Simian Immunodeficiency Virus Enhance RNA Encapsidation 英文参考文献.doc

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Rev Proteins of Human and Simian Immunodeficiency Virus Enhance RNA Encapsidation 英文参考文献

RevProteinsofHumanandSimian ImmunodeficiencyVirus EnhanceRNAEncapsidation Sabine Brandt[,Maik Bli?enbach[,Bastian Grewe, Rebecca Konietzny, Thomas Grunwald, Klaus Uberla¨ * DepartmentofMolecularandMedicalVirology,Ruhr-UniversityBochum,Germany ThemainfunctionattributedtotheRevproteinsofimmunodeficiencyvirusesistheshuttlingofviralRNAscontaining the Rev responsive element (RRE) via the CRM-1 export pathway from the nucleus to the cytoplasm. This restricts expressionofstructuralproteinstothelatephaseofthelentiviralreplicationcycle.UsingRev-independent gag-pol expressionplasmidsofHIV-1andsimianimmunodeficiencyvirusandlentiviralvectorconstructs,wehaveobserved thatHIV-1andsimianimmunodeficiencyvirusRevenhancedRNAencapsidation20-to70-fold,correlatingwellwith the effect of Rev on vector titers. In contrast, cytoplasmic vector RNA levels were only marginally affected by Rev. Binding of Rev to the RRE or to a heterologous RNA element was required for Rev-mediated enhancement of RNA encapsidation. In addition to specific interactions of nucleocapsid with the packaging signal at the 59 end of the genome, the Rev/RRE system provides a second mechanism contributing to preferential encapsidation of genomic lentiviralRNA. Citation:BrandtS,Bli?enbachM,GreweB,KonietznyR,GrunwaldT,etal.(2007)RevproteinsofhumanandsimianimmunodeficiencyvirusenhanceRNAencapsidation. PLoSPathog3(4):e54.doi:10.1371/journal.ppat.0030054 potential mechanism, a direct interaction between nascent Gag and its RNA template has been proposed [6]. Ef?cient Introduction Virus particles of HIV-1, the major cause of the AIDS epidemic, and other members of the lentivirus family of retroviruses contain an RNA genome. After viral entry, the genomicRNAisreversetranscribedintoDNAandintegrates intothegenomeofthehostcell.TheintegratedproviralDNA is transcribed by RNA polymerase II. Complex alternative splicing events with a major splice donor in the 59 untranslated region (UTR) generate viral mRNAs encoding