RNA aptamer‐mediated interference of HCV replication by targeting the CRE‐5BSL3.2 domain

Marton, Soledad; Romero-López, Cristina; Berzal‐Herranz, Alfredo

doi:10.1111/j.1365-2893.2012.01629.x

Cited by 18 publications

(19 citation statements)

References 45 publications

(95 reference statements)

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“…They also provide an interesting means of developing molecular tools for deciphering the functional role of genomic structural elements, and therefore the identification of potential therapeutic targets. This has already been shown for other, closely related viruses such as HCV (Marton et al, 2011, 2013; Fernández-Sanlés et al, 2015) as well as non-related viruses such as HIV (Sánchez-Luque et al, 2014). Aptamers can be chemically modified quite easily to increase their stability and improve their efficiency.…”

Section: Nucleic Acids Targeting Flavivirus Genomessupporting

confidence: 57%

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

et al. 2017

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The genus Flavivirus comprises a large number of small, positive-sense single-stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod and/or vertebrate host cells. The genus, which has some 70 member species, includes a number of emerging and re-emerging pathogens responsible for outbreaks of human disease around the world, such as the West Nile, dengue, Zika, yellow fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis viruses. Like other RNA viruses, flaviviruses have a compact RNA genome that efficiently stores all the information required for the completion of the infectious cycle. The efficiency of this storage system is attributable to supracoding elements, i.e., discrete, structural units with essential functions. This information storage system overlaps and complements the protein coding sequence and is highly conserved across the genus. It therefore offers interesting potential targets for novel therapeutic strategies. This review summarizes our knowledge of the features of flavivirus genome functional RNA domains. It also provides a brief overview of the main achievements reported in the design of antiviral nucleic acid-based drugs targeting functional genomic RNA elements.

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Section: Nucleic Acids Targeting Flavivirus Genomessupporting

confidence: 57%

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

et al. 2017

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“…In the latter work, the binding of hnRNPA1 to the 5′ and 3′UTR (downstream of CRE) was also shown. Since CRE plays a role in both NS5B binding 49 and in viral 5′-3′contacts 21 22 , one might hypothesize that the binding of hnRNPA1 to CRE would have an effect on HCV replication. In the present work, hnRNPA1 clearly downregulates HCV replication, one explanation could be that this protein competes with NS5B for CRE binding, thus reducing the efficiency of the viral polymerase.…”

Section: Discussionmentioning

confidence: 99%

The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation

Ríos-Marco

Romero-López

Berzal‐Herranz

2016

Sci Rep

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The cis-acting replication element (CRE) of the hepatitis C virus (HCV) RNA genome is a region of conserved sequence and structure at the 3′ end of the open reading frame. It participates in a complex and dynamic RNA-RNA interaction network involving, among others, essential functional domains of the 3′ untranslated region and the internal ribosome entry site located at the 5′ terminus of the viral genome. A proper balance between all these contacts is critical for the control of viral replication and translation, and is likely dependent on host factors. Proteomic analyses identified a collection of proteins from a hepatoma cell line as CRE-interacting candidates. A large fraction of these were RNA-binding proteins sharing highly conserved RNA recognition motifs. The vast majority of these proteins were validated by bioinformatics tools that consider RNA-protein secondary structure. Further characterization of representative proteins indicated that hnRNPA1 and HMGB1 exerted negative effects on viral replication in a subgenomic HCV replication system. Furthermore DDX5 and PARP1 knockdown reduced the HCV IRES activity, suggesting an involvement of these proteins in HCV translation. The identification of all these host factors provides new clues regarding the function of the CRE during viral cycle progression.

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“…To inhibit HCV replication, Marton et al selected RNA aptamers against CRE element that were able to repress replication of HCV replicon in hepatic cells [98]. Subsequently, two selected aptamers, P58 and P78, interact with subdomain 5BSL3.2 of the CRE element and produce a structural reorganization of the 3′ end HCV genome and a significant decrease of HCV replication in vivo [99]. …”

Section: Aptamers For Virus Diagnosis and Treatmentmentioning

confidence: 99%

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

González

Martı́n

Fernández³

et al. 2016

Pharmaceuticals

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Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment.

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RNA aptamer‐mediated interference of HCV replication by targeting the CRE‐5BSL3.2 domain

Cited by 18 publications

References 45 publications

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

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