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RNA aptamer‐mediated interference of HCV replication by targeting the CRE‐5BSL3.2 domain
Author(s) -
Marton S.,
RomeroLópez C.,
BerzalHerranz A.
Publication year - 2013
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2012.01629.x
Subject(s) - ns5b , subgenomic mrna , rna , aptamer , biology , rna dependent rna polymerase , viral replication , virology , hepatitis c virus , rna interference , computational biology , genetics , microbiology and biotechnology , virus , gene , hepacivirus
Summary. The RNA genome of hepatitis C virus (HCV) contains multiple conserved structural RNA domains that play key roles in essential viral processes. A conserved structural component within the 3′ end of the region coding for viral RNA‐dependent RNA polymerase (NS5B) has been characterized as a functional cis ‐acting replication element (CRE). This study reports the ability of two RNA aptamers, P‐58 and P‐78, to interfere with HCV replication by targeting the essential 5BSL3.2 domain within this CRE. Structure‐probing assays showed the binding of the aptamers to the CRE results in a structural reorganization of the apical portion of the 5BSL3.2 stem‐loop domain. This interfered with the binding of the NS5B protein to the CRE and induced a significant reduction in HCV replication (≈50%) in an autonomous subgenomic HCV replication system. These results highlight the potential of this CRE as a target for the development of anti‐HCV therapies and underscore the potential of antiviral agents based on RNA aptamer molecules.