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Research Paper
Endogenous Expression of an Anti-TAR Aptamer Reduces HIV-1 Replication
Gaëlle Kolb, Sandrine Reigadas, Daniela Castanotto, Aurélie Faure, Michel Ventura, John J. Rossi and Jean J. Toulme
volume 3 | issue 4
october/november/december 2006Pages: 150 - 156
This is an open-access article
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An anti-TAR RNA aptamer called R06, which binds tightly and specifically to the trans-activation responsive (TAR) element of the human immunodeficiency virus type 1 (HIV-1) through loop-loop interactions has been previously selected1. We used HIV-based retroviral vectors to express the R06 aptamer. Its synthesis was driven by the U16 snoRNA. We investigated the ability of this cassette to interfere with TAR-mediated transcription using HeLa P4 cells stably expressing the β-galactosidase gene under the control of the HIV-1 5’LTR. We demonstrated that, upon HIV-1 infection, the β-galactosidase activity was reduced in cells expressing the nucleolar U16-R06 transcript. The replication of HIV-1 in these cells was also reduced as shown by quantification of the HIV-1 protease gene 24 h post-infection. This effect was specific and related to the formation of R06 TAR complex as an aptamer with a mutated loop, which was no longer able to bind to TAR, did not show any effect. The nucleolus is likely a compartment of interest for targeting the TAR-protein complex responsible for the trans-activation of transcription of the HIV-1 genome.
Authors
Gaëlle Kolb
INSERM and Université Victor Segalen Bordeaux; Bordeaux, France
Sandrine Reigadas
INSERM and Université Victor Segalen Bordeaux; Bordeaux, France
Daniela Castanotto
Beckam Research Institute of the City of Hope; Duarte, California USA
Aurélie Faure
CNRS, Université Victor Segalen Bordeaux; Bordeaux, France
Michel Ventura
CNRS, Université Victor Segalen Bordeaux; Bordeaux, France
John J. Rossi
Beckam Research Institute of the City of Hope; Duarte, California USA
Jean J. Toulme
Université Victor Segalen Bordeaux; Bordeaux, France
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.