Titre

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

Type
abstract de conférence/colloque
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Série
Swiss Medical Weekly
Auteur(s)
Gouttenoire, J.
Auteure/Auteur
Kennel, A.
Auteure/Auteur
di Pietro, A.
Auteure/Auteur
Penin, F.
Auteure/Auteur
Moradpour, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
Titre du livre ou conférence/colloque
Annual Meeting of the Swiss Society of Gastroenterology, Swiss Society for Visceral Surgery, Swiss Association for the Study of the Liver
Adresse
Lausanne, Switzerland, September 29-30, 2011
ISBN
1424-7860
Statut éditorial
Publié
Date de publication
2011
Volume
141
Première page
16S
Peer-reviewed
Oui
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.
PID Serval
serval:BIB_2F5CDA392335
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URL éditeur
Date de création
2012-01-03T13:30:10.389Z
Date de création dans IRIS
2025-05-20T14:00:49Z