scholarly journals A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti–hepatitis C target

2016 ◽  
Vol 2 (4) ◽  
pp. e1501535 ◽  
Author(s):  
Shao-Ru Wang ◽  
Yuan-Qin Min ◽  
Jia-Qi Wang ◽  
Chao-Xing Liu ◽  
Bo-Shi Fu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Consensus Sequence ◽  
Protein Translation ◽  
Core Gene ◽  
Consensus Sequences ◽  
Virus Core ◽  
New Strategy ◽  
Inhibit Protein Translation

G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the high genetic variability of this ribovirus; we further show using various methods that such consensus sequences can fold into unimolecular G4 RNA structures, both in vitro and under physiological conditions. Furthermore, we provide direct evidences that small molecules specifically targeting G4 can stabilize this structure to reduce RNA replication and inhibit protein translation of intracellular hepatitis C. Ultimately, the stabilization of G4 RNA in the genome of hepatitis C represents a promising new strategy for anti–hepatitis C drug development.

scholarly journals Expression of the Novel Hepatitis C Virus Core+1/ARF Protein in the Context of JFH1-Based Replicons

2015 ◽  
Vol 89 (9) ◽  
pp. 5164-5170 ◽  
Author(s):  
Ioly Kotta-Loizou ◽  
Ioannis Karakasiliotis ◽  
Niki Vassilaki ◽  
Panagiotis Sakellariou ◽  
Ralf Bartenschlager ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Gene ◽  
Open Reading Frame ◽  
The Novel ◽  
Reading Frame ◽  
The Core ◽  
Virus Core ◽  
First Time ◽  
Arf Protein

Hepatitis C virus contains a second open reading frame within the core gene, designated core+1/ARF. Here we demonstrate for the first time expression of core+1/ARF protein in the context of a bicistronic JFH1-based replicon and report the production of two isoforms, core+1/L (long) and core+1/S (short), with different kinetics.

scholarly journals The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model

Gut ◽  
2007 ◽  
Vol 56 (9) ◽  
pp. 1302-1308 ◽  
Author(s):  
C Hourioux ◽  
R Patient ◽  
A Morin ◽  
E Blanchard ◽  
A Moreau ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Cellular Model ◽  
Genotype 3 ◽  
Virus Core

scholarly journals Lipidation of T helper sequences from hepatitis C virus core significantly enhances T-cell activity in vitro

Immunology ◽  
2001 ◽  
Vol 102 (4) ◽  
pp. 460-465 ◽  
Author(s):  
B. Langhans ◽  
I. Braunschweiger ◽  
S. Schweitzer ◽  
G. Jung ◽  
G. Inchauspe ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Activity ◽  
T Helper ◽  
Virus Core

scholarly journals Lack of Association between Hepatitis C Virus core Gene Variation 70/91aa and Insulin Resistance

2017 ◽  
Vol 18 (7) ◽  
pp. 1444 ◽  
Author(s):  
Letícia Scalioni ◽  
Allan da Silva ◽  
Juliana Miguel ◽  
Márcia Espírito Santo ◽  
Vanessa Marques ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Gene ◽  
Gene Variation ◽  
Virus Core

scholarly journals Evidence for a functional RNA element in the hepatitis C virus core gene

2007 ◽  
Vol 104 (8) ◽  
pp. 2879-2884 ◽  
Author(s):  
L. K. McMullan ◽  
A. Grakoui ◽  
M. J. Evans ◽  
K. Mihalik ◽  
M. Puig ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Gene ◽  
Virus Core ◽  
Functional Rna

scholarly journals Future Directions in the Treatment of Patients with Chronic Hepatitis C Virus Infection

1999 ◽  
Vol 13 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Robert G Gish
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Throughput Screening ◽  
In Vitro Model ◽  
Single Agent ◽  
Protein Translation ◽  
In Vitro Translation ◽  
Biotechnology Companies ◽  
Vitro Model

Hepatitis C virus (HCV) infects over 170 million people worldwide. While interferon is currently the most used single agent therapy, this drug may result in a sustained loss of virus from the blood in only up to 15% of patients; new options for treatment are needed. With the release of ribavirin in North America and Europe, a viral clearance rate or ‘cure’ may be attained in up to 40% of patients. Developing successful antiviral therapy that prevents or delays the development of cirrhosis, liver failure and liver cancer as well as decreasing the demand for liver transplantation are clearly identified goals. Unfortunately, there is no complete in vitro model of HCV replication or translation. Due to the lack of an animal or cell culture model of HCV infection, in vitro translation screening systems to identify inhibitors of HCV protein translation are being evaluated by a large number of biotechnology companies. With advancing computer technology, high throughput screening processes are now possible and can be joined to specific in vitro model testing systems. Along with examining some of the information known about HCV therapy and the HCV genome, the present review discusses potential targets for new therapies and identifies therapeutic agents that are nearing clinical application

scholarly journals Hepatitis C Virus Core Protein Interacts with 14-3-3 Protein and Activates the Kinase Raf-1

2000 ◽  
Vol 74 (4) ◽  
pp. 1736-1741 ◽  
Author(s):  
Hiroshi Aoki ◽  
Junpei Hayashi ◽  
Mitsuhiko Moriyama ◽  
Yasuyuki Arakawa ◽  
Okio Hino
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Growth Regulation ◽  
Core Protein ◽  
Dependent Manner ◽  
Kinase Activation ◽  
Virus Core ◽  
Hcv Core Protein

ABSTRACT Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver dysfunction in humans and is epidemiologically closely associated with the development of human hepatocellular carcinoma. Among HCV components, core protein has been reported to be implicated in cell growth regulation both in vitro and in vivo, although mechanisms explaining those effects are still unclear. In the present study, we identified that members of the 14-3-3 protein family associate with HCV core protein. 14-3-3 protein bound to HCV core protein in a phosphoserine-dependent manner. Introduction of HCV core protein caused a substantial increase in Raf-1 kinase activity in HepG2 cells and in a yeast genetic assay. Furthermore, the HCV core–14-3-3 interaction was essential for Raf-1 kinase activation by HCV core protein. These results suggest that HCV core protein may represent a novel type of Raf-1 kinase-activating protein through its interaction with 14-3-3 protein and may contribute to hepatocyte growth regulation.

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