Showing papers by "Nadia Naffakh published in 2006"
TL;DR: The data indicate that genetic variation in the absence of any drug-selective pressure may result in significant variations in sensitivity to anti-NA drugs, and underscores the need for continuous evaluation of the impact of genetic drift on this parameter, especially for influenza viruses with pandemic potential.
Abstract: Geographic spread of highly pathogenic avian H5N1 influenza viruses may give rise to an influenza pandemic. During the first months of a pandemic, control measures would rely mainly on antiviral drugs, such as the neuraminidase (NA) inhibitors oseltamivir and zanamivir. In this study, we compare the sensitivities to oseltamivir of the NAs of several highly pathogenic H5N1 viruses isolated in Asia from 1997 to 2005. The corresponding 50% inhibitory concentrations were determined using a standard in vitro NA inhibition assay. The Km for the substrate and the affinity for the inhibitor (Ki) of NA were determined for a 1997 and a 2005 virus, using an NA inhibition assay on cells transiently expressing the viral enzyme. Our data show that the sensitivities of the NAs of H5N1 viruses isolated in 2004 and 2005 to oseltamivir are about 10-fold higher than those of earlier H5N1 viruses or currently circulating H1N1 viruses. Three-dimensional modeling of the N1 protein predicted that Glu248Gly and Tyr252His changes could account for increased sensitivity. Our data indicate that genetic variation in the absence of any drug-selective pressure may result in significant variations in sensitivity to anti-NA drugs. Although the clinical relevance of a 10-fold increase in the sensitivity of NA to oseltamivir needs to be investigated further, the possibility that sensitivity to anti-NA drugs could increase (or possibly decrease) significantly, even in the absence of treatment, underscores the need for continuous evaluation of the impact of genetic drift on this parameter, especially for influenza viruses with pandemic potential.
94 citations
TL;DR: Intranasal immunization of mice with live vNA38 viruses induced B and T cell responses specific for the heterologous protein expressed, establishing the usefulness of such recombinant influenza viruses with a dicistronic segment for the development of live bivalent vaccines.
21 citations
Journal Article•
TL;DR: Les systemes de genetique inverse a base de plasmides sont desormais largement utilises, which facilitent l’etude des mecanismes moleculaires de the replication et de the pathogenicite des virus grippaux.
Abstract: La mise au point d’un systeme de genetique inverse permettant de produire des virus grippaux recombinants a partir d’ADNc clones s’est averee difficile. La difficulte tenait probablement a la nature du genome viral, constitue de plusieurs segments d’ARN de polarite negative et devant etre associe a la nucleoproteine et au complexe polymerase pour etre infectieux. C’est l’utilisation d’un systeme de transcription dependant de l’ARN polymerase I et la co-transfection de 12 ou de 8 plasmides qui a finalement permis, a la fin des annees 1990, la reconstitution des huit ribonucleoproteines d’un virus grippal de type A dans une meme cellule et la production de virus recombinants. Les systemes de genetique inverse a base de plasmides sont desormais largement utilises. Ils facilitent l’etude des mecanismes moleculaires de la replication et de la pathogenicite des virus grippaux. Ils sont egalement tres utiles dans le champ de la vaccination antigrippale, offrant en particulier la possibilite de concevoir de nouveaux types de vaccins vivants attenues et des vaccins pandemiques. Ils ouvrent enfin la voie a l’utilisation des virus grippaux comme vecteurs d’expression d’un antigene heterologue, dans un but prophylactique ou therapeutique.
2 citations