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

Détails

ID Serval
serval:BIB_2F5CDA392335
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
Functional Characterization of a n NTPase Activity of the Hepatitis C Virus Nonstructural Protein 4B
Titre de la conférence
Annual Meeting of the Swiss Society of Gastroenterology, Swiss Society for Visceral Surgery, Swiss Association for the Study of the Liver
Auteur(s)
Gouttenoire J., Kennel A., di Pietro A., Penin F., Moradpour D.
Adresse
Lausanne, Switzerland, September 29-30, 2011
ISBN
1424-7860
ISSN-L
0036-7672
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
141
Série
Swiss Medical Weekly
Pages
16S
Langue
anglais
Résumé
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.
Création de la notice
03/01/2012 15:30
Dernière modification de la notice
20/08/2019 14:13
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