Interfering with hepatitis C virus IRES activity using RNA molecules identified by a novel in vitro selection method

2005 ◽  
Vol 386 (2) ◽  
Author(s):  
Cristina Romero-López ◽  
Alicia Barroso-delJesus ◽  
Elena Puerta-Fernández ◽  
Alfredo Berzal-Herranz
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Selection ◽  
Selection Method ◽  
Rna Molecules

scholarly journals In Vitro Selection and Characterization of Hepatitis C Virus Serine Protease Variants Resistant to an Active-Site Peptide Inhibitor

2003 ◽  
Vol 77 (6) ◽  
pp. 3669-3679 ◽  
Author(s):  
Caterina Trozzi ◽  
Linda Bartholomew ◽  
Alessandra Ceccacci ◽  
Gabriella Biasiol ◽  
Laura Pacini ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Serine Protease ◽  
In Vitro Selection ◽  
Three Dimensional ◽  
Host Cells ◽  
Dimensional Structure ◽  
In Vitro Systems

ABSTRACT The hepatitis C virus (HCV) serine protease is necessary for viral replication and represents a valid target for developing new therapies for HCV infection. Potent and selective inhibitors of this enzyme have been identified and shown to inhibit HCV replication in tissue culture. The optimization of these inhibitors for clinical development would greatly benefit from in vitro systems for the identification and the study of resistant variants. We report the use HCV subgenomic replicons to isolate and characterize mutants resistant to a protease inhibitor. Taking advantage of the replicons' ability to transduce resistance to neomycin, we selected replicons with decreased sensitivity to the inhibitor by culturing the host cells in the presence of the inhibitor and neomycin. The selected replicons replicated to the same extent as those in parental cells. Sequence analysis followed by transfection of replicons containing isolated mutations revealed that resistance was mediated by amino acid substitutions in the protease. These results were confirmed by in vitro experiments with mutant enzymes and by modeling the inhibitor in the three-dimensional structure of the protease.

scholarly journals In vitro selection of RNA aptamers that bind the RNA-dependent RNA polymerase of hepatitis C virus: A possible role of GC-rich RNA motifs in NS5B binding

Virology ◽  
2009 ◽  
Vol 388 (1) ◽  
pp. 91-102 ◽  
Author(s):  
Hiroshi Kanamori ◽  
Kazuhito Yuhashi ◽  
Yasutoshi Uchiyama ◽  
Tatsuhiko Kodama ◽  
Shin Ohnishi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Polymerase ◽  
In Vitro Selection ◽  
Rna Aptamers ◽  
Rna Dependent Rna Polymerase ◽  
Rna Motifs ◽  
Selection Of

scholarly journals Self-Assembly of Nucleocapsid-Like Particles from Recombinant Hepatitis C Virus Core Protein

2001 ◽  
Vol 75 (5) ◽  
pp. 2119-2129 ◽  
Author(s):  
Meghan Kunkel ◽  
Marta Lorinczi ◽  
René Rijnbrand ◽  
Stanley M. Lemon ◽  
Stanley J. Watowich
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Self Assembly ◽  
High Throughput Screening ◽  
Core Protein ◽  
Rna Molecules ◽  
The Core ◽  
Assembly Pathway ◽  
Core Proteins

ABSTRACT Little is known about the assembly pathway and structure of hepatitis C virus (HCV) since insufficient quantities of purified virus are available for detailed biophysical and structural studies. Here, we show that bacterially expressed HCV core proteins can efficiently self-assemble in vitro into nucleocapsid-like particles. These particles have a regular, spherical morphology with a modal distribution of diameters of approximately 60 nm. Self-assembly of nucleocapsid-like particles requires structured RNA molecules. The 124 N-terminal residues of the core protein are sufficient for self-assembly into nucleocapsid-like particles. Inclusion of the carboxy-terminal domain of the core protein modifies the core assembly pathway such that the resultant particles have an irregular outline. However, these particles are similar in size and shape to those assembled from the 124 N-terminal residues of the core protein. These results provide novel opportunities to delineate protein-protein and protein-RNA interactions critical for HCV assembly, to study the molecular details of HCV assembly, and for performing high-throughput screening of assembly inhibitors.

scholarly journals In vitro selection of a neutralization-resistant hepatitis C virus escape mutant

2008 ◽  
Vol 105 (49) ◽  
pp. 19450-19455 ◽  
Author(s):  
M. Gal-Tanamy ◽  
Z.-Y. Keck ◽  
M. Yi ◽  
J. A. McKeating ◽  
A. H. Patel ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Selection ◽  
Escape Mutant ◽  
Virus Escape ◽  
Virus Escape Mutant ◽  
Selection Of

Funktion von CEACAM-1 im Rahmen der Therapie der Hepatitis C-Virus Infektion mit Interferon-alpha in vivo und in vitro

2006 ◽  
Vol 44 (08) ◽  
Author(s):  
P Hilgard ◽  
R Bröring ◽  
M Trippler ◽  
S Viazov ◽  
G Gerken ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha
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