Functional analyses reveal extensive RRE plasticity in primary HIV-1 sequences selected under selective pressure

PloS One
Francesc CunyatCecilia Cabrera

Abstract

HIV-1 Rev response element (RRE) is a functional region of viral RNA lying immediately downstream to the junction of gp120 and gp41 in the env coding sequence. The RRE is essential for HIV replication and binds with the Rev protein to facilitate the export of viral mRNA from nucleus to cytoplasm. It has been suggested that changes in the predicted secondary structure of primary RRE sequences impact the function of the RREs; however, functional assays have not yet been performed. The aim of this study was to characterize the genetic, structural and functional variation in the RRE primary sequences selected in vivo by Enfuvirtide pressure. Multiple RRE variants were obtained from viruses isolated from patients who failed an Enfuvirtide-containing regimen. Different alterations were observed in the predicted RRE secondary structures, with the abrogation of the primary Rev binding site in one of the variants. In spite of this, most of the RRE variants were able to bind Rev and promote the cytoplasmic export of the viral mRNAs with equivalent efficiency in a cell-based assay. Only RRE45 and RRE40-45 showed an impaired ability to bind Rev in a gel-shift binding assay. Unexpectedly, this impairment was not reflected in functional capa...Continue Reading

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Jun 16, 2015·Viruses·Jason W Rausch, Stuart F J Le Grice
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Methods Mentioned

BETA
PCR
electrophoretic
in vitro transcription
transfection
Assay
transfections
PCRs
enzyme-linked immunosorbent assay
electrophoretic mobility shift assay
electro-mobility shift assay

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