ArticleCellular and molecular life sciences : CMLS2015
Mutations of the SL2 dimerization sequence of the hepatitis C genome abrogate viral replication.
Article in Cellular and molecular life sciences : CMLS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Conformational dynamics of the hepatitis C virus 3'X RNA.RNA (New York, N.Y.) · 2024Article
- Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p.RNA (New York, N.Y.) · 2023Article
- Dimerization of an umbravirus RNA genome activates subgenomic mRNA transcription.Nucleic acids research · 2023Article
- Inter- and Intramolecular RNA-RNA Interactions Modulate the Regulation of Translation Mediated by the 3' UTR in West Nile Virus.International journal of molecular sciences · 2023Article
- The low-resolution structural models of hepatitis C virus RNA subdomain 5BSL3.2 and its distal complex with domain 3'X point to conserved regulatory mechanisms within the Flaviviridae family.Nucleic acids research · 2022Article
- Integrating single-molecule FRET and biomolecular simulations to study diverse interactions between nucleic acids and proteins.Essays in biochemistry · 2021Review
- The Role of the RNA-RNA Interactome in the Hepatitis C Virus Life Cycle.International journal of molecular sciences · 2020Review
- Structure and function analysis of the essential 3'X domain of hepatitis C virus.RNA (New York, N.Y.) · 2020Article
- The HCV genome domains 5BSL3.1 and 5BSL3.3 act as managers of translation.Scientific reports · 2018Article
- Form confers function: Case of the 3'X region of the hepatitis C virus genome.World journal of gastroenterology · 2018Review
- RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand.Scientific reports · 2018Article
- An unexpected RNA distal interaction mode found in an essential region of the hepatitis C virus genome.Nucleic acids research · 2018Article
- Three-dimensional structure of the 3'X-tail of hepatitis C virus RNA in monomeric and dimeric states.RNA (New York, N.Y.) · 2017Article
- The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization.Scientific reports · 2017Article
- The 5BSL3.2 Functional RNA Domain Connects Distant Regions in the Hepatitis C Virus Genome.Frontiers in microbiology · 2017Review
- The conserved 3'X terminal domain of hepatitis C virus genomic RNA forms a two-stem structure that promotes viral RNA dimerization.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem-loop SL2 is a self-interacting palindromic sequence that has been identified within the hepatitis C virus genome (HCV). While, RNA dimerization of the HCV genome has been observed in vitro with short RNA sequences, the role of a putative RNA dimerization during viral replication has not been elucidated. To determine the effect of genomic dimerization on viral replication, we introduced mutations into SL2 predicted to disrupt genomic dimerization. Using surface plasmon resonance, we show that mutations within the SL2 bulge impact dimerization in vitro. Transfection of Huh7 cells with luciferase-encoding full-length genomes containing SL2 mutations abolishes viral replication. Luciferase expression indicates that viral translation is not or slightly affected and that the viral RNA is properly encapsidated. However, RT-qPCR analysis demonstrates that viral RNA synthesis is drastically decreased. In vitro synthesis experiments using the viral recombinant polymerase show that modifications of intra-molecular interactions have no effect on RNA synthesis, while impairing inter-molecular interactions decreases polymerase activity. This confirms that dimeric templates are preferentially replicated by the viral polymerase. Altogether, these results indicate that the dimerization of the HCV genomic RNA is a crucial step for the viral life cycle especially for RNA replication. RNA dimerization could explain the existence of HCV recombinants in cell culture and patients reported recently in other studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.