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Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs
Instituto de Parasitología y Biomedicina “López-Neyra”, CSIC, P.T. Ciencias de la Salud, Av. del Conocimiento s/n, Armilla, 18100 Granada, Spain
Instituto de Bioquímica Vegetal y Fotosíntesis, Universidad de Sevilla-CSIC. Américo Vespucio s/n, Isla de la Cartuja, 41092 Sevilla, Spain
* Author to whom correspondence should be addressed.
Received: 31 May 2010; in revised form: 28 June 2010 / Accepted: 1 July 2010 / Published: 7 July 2010
Abstract: The 5’-untranslated region (5’UTR) of the HIV-1 RNA is an attractive target for engineered ribozymes due to its high sequence and structural conservation. This region encodes several conserved structural RNA domains essential in key processes of the viral replication and infection cycles. This paper reports the inhibitory effects of catalytic antisense RNAs composed of two inhibitory RNA domains: an engineered ribozyme targeting the 5’ UTR and a decoy or antisense domain of the dimerization initiation site (DIS). These chimeric molecules are able to cleave the HIV-1 5’UTR efficiently and prevent viral genome dimerization in vitro. Furthermore, catalytic antisense RNAs inhibited viral production up to 90% measured as p24 antigen levels in ex vivo assays. The use of chimeric RNA molecules targeting different domains represents an attractive antiviral strategy to be explored for the prevention of side effects from current drugs and of the rapid emergence of escape variants of HIV-1.
Keywords: Ribozymes; antisense RNAs; HIV-1 RNA dimerization; anti-HIV RNAs
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Sánchez-Luque, F.J.; Reyes-Darias, J.A.; Puerta-Fernández, E.; Berzal-Herranz, A. Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs. Molecules 2010, 15, 4757-4772.
Sánchez-Luque FJ, Reyes-Darias JA, Puerta-Fernández E, Berzal-Herranz A. Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs. Molecules. 2010; 15(7):4757-4772.
Sánchez-Luque, Francisco J.; Reyes-Darias, José A.; Puerta-Fernández, Elena; Berzal-Herranz, Alfredo. 2010. "Inhibition of HIV-1 Replication and Dimerization Interference by Dual Inhibitory RNAs." Molecules 15, no. 7: 4757-4772.