Functional Characterization of a n NTPase Activity of the Hepatitis C Virus Nonstructural Protein 4B

Details

Serval ID
serval:BIB_2F5CDA392335
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Title
Functional Characterization of a n NTPase Activity of the Hepatitis C Virus Nonstructural Protein 4B
Title of the conference
Annual Meeting of the Swiss Society of Gastroenterology, Swiss Society for Visceral Surgery, Swiss Association for the Study of the Liver
Author(s)
Gouttenoire J., Kennel A., di Pietro A., Penin F., Moradpour D.
Address
Lausanne, Switzerland, September 29-30, 2011
ISBN
1424-7860
ISSN-L
0036-7672
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
141
Series
Swiss Medical Weekly
Pages
16S
Language
english
Abstract
Background: Nonstructural p rotein 4 B (NS4B) i s the m asterorganizer of hepatitis C virus (HCV) replication complexformation. It is a multispanning membrane protein that has beenreported to p ossess NTPase activity. This enzymatic functionhas been poorly studied so far and its role in the HCV life cycleis u nknown. T he present w ork-in-progress a ims at validatingand functionally c haracterizing this a ctivity a nd its r ole in t heviral life cycle.Methods: B ioinformatic analyses were performed to i dentifykey residues for site-directed mutagenesis, both in t he contextof s ubgenomic r eplicons a s well as recombinant v iruses.Mutants were investigated with respect to R NA replication andinfectious particle p roduction. In p arallel, expression andpurification of recombinant wild-type and mutant NS4B proteinsare being pursued to characterize enzymatic activity in vitro.Results: B ioinformatic a nalyses revealed t hat p redictedNTPase features are conserved only in H CV NS4B b ut n ot i nNS4B from other Flaviviridae f amily m embers. A laninesubstitutions were designed to target predicted key Walker A, Band C motifs. These substitutions affected RNA replication andinfectious virus production to v arying degrees. Optimization ofrecombinant protein production is i n progress both in b acterialas well as mammalian expression systems.Conclusions: These studies should yield new insights into thefunctions of this hitherto poorly characterized viral nonstructuralprotein and may reveal novel targets for antiviral intervention inthe future.
Create date
03/01/2012 15:30
Last modification date
20/08/2019 14:13
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