RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand. Sci Rep 2018 May 25;8(1):8120
Date
05/29/2018Pubmed ID
29802381Pubmed Central ID
PMC5970142DOI
10.1038/s41598-018-26582-3Scopus ID
2-s2.0-85066875967 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
DNA and RNA guanine-rich oligonucleotides can form non-canonical structures called G-quadruplexes or "G4" that are based on the stacking of G-quartets. The role of DNA and RNA G4 is documented in eukaryotic cells and in pathogens such as viruses. Yet, G4 have been identified only in a few RNA viruses, including the Flaviviridae family. In this study, we analysed the last 157 nucleotides at the 3'end of the HCV (-) strand. This sequence is known to be the minimal sequence required for an efficient RNA replication. Using bioinformatics and biophysics, we identified a highly conserved G4-prone sequence located in the stem-loop IIy' of the negative strand. We also showed that the formation of this G-quadruplex inhibits the in vitro RNA synthesis by the RdRp. Furthermore, Phen-DC3, a specific G-quadruplex binder, is able to inhibit HCV viral replication in cells in conditions where no cytotoxicity was measured. Considering that this domain of the negative RNA strand is well conserved among HCV genotypes, G4 ligands could be of interest for new antiviral therapies.
Author List
Jaubert C, Bedrat A, Bartolucci L, Di Primo C, Ventura M, Mergny JL, Amrane S, Andreola MLAuthor
Amina Bedrat PhD Postdoctoral Researcher 3 in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Base SequenceCell Line
Conserved Sequence
G-Quadruplexes
Hepacivirus
Humans
RNA, Viral
Virus Replication