Endogenous Expression of an Anti-TAR Aptamer Reduces HIV-1 Replication

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....

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Bibliographic Details
Published in:RNA (Cambridge) 2006-10, Vol.3 (4), p.150-156
Main Authors: Kolb, Gaëlle, Reigadas, Sandrine, Castanotto, Daniela, Faure, Aurélie, Ventura, Michel, Rossi, John J., Toulme, Jean J.
Format: Article
Language:English
Subjects:
Anti-HIV Agents - chemistry
Anti-HIV Agents - metabolism
Aptamers, Nucleotide - biosynthesis
Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - genetics
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cycle
Gene Expression Regulation, Viral - physiology
HeLa Cells
HIV Long Terminal Repeat - genetics
HIV-1 - chemistry
HIV-1 - genetics
HIV-1 - physiology
Humans
Landes
Life Sciences
Microbiology and Parasitology
Organogenesis
Proteins
Transcriptional Activation - genetics
Virus Replication - genetics
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Summary: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.
ISSN:1547-6286
1355-8382
1555-8584
1469-9001
DOI:10.4161/rna.3.4.3811