Sensitivity of influenza viruses to zanamivir and oseltamivir: A study performed on viruses circulating in France prior to the introduction of neuraminidase inhibitors in clinical practice

Ferraris, Olivier; Keßler, Nicole; Lina, Bruno

doi:10.1016/j.antiviral.2005.07.004

Cited by 75 publications

(54 citation statements)

References 30 publications

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“…Interestingly, four out of these seven outliers were isolated in the same span of time (2001 to 2004) in which oseltamivir was put into use (1999). Other investigators have determined baseline levels of susceptibility to oseltamivir, but only among human influenza isolates after NAIs were put into clinical use (14,20,23,24,32,33,39). We found small differences in the mean IC 50 s for the inhibition of avian and swine influenza virus N1 NAs for isolates from 1979 to 2008.…”

Section: Discussionmentioning

confidence: 68%

Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype

Stoner

Krauss

DuBois

et al. 2010

J Virol

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Section: Discussionmentioning

confidence: 68%

Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype

Stoner

Krauss

DuBois

et al. 2010

J Virol

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“…After a last step of washings, glycerol buffer (0.042% Na 2 NA activity and inhibition assays. Fluorimetric NA activity assays were done as described by Ferraris et al (19). Total NA activities were calculated as the quantity of 2Ј-(4-methylumbelliferyl)-␣-D-N-acetylneuraminic acid (MUN) substrate degraded in 1 h per ml of viral suspensions (nmol/h/ml).…”

Section: ϫ4mentioning

confidence: 99%

“…The NA activity inhibition assay was performed as described by Ferraris et al (19) using a standardized dose of NA activity (10 nmol/h/ml). The 50% inhibitory concentrations (IC 50 s) of antiviral drugs were calculated according to the concentration required for reducing NA activity by 50% by analysis with Sigma Plot software.…”

Section: ϫ4mentioning

confidence: 99%

Combinatorial Effect of Two Framework Mutations (E119V and I222L) in the Neuraminidase Active Site of H3N2 Influenza Virus on Resistance to Oseltamivir

Richard

Ferraris

Erny

et al. 2011

Antimicrob Agents Chemother

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Neuraminidase (NA) inhibitors (NIs) are the first line of defense against influenza virus. Reverse genetics experiments allow the study of resistance mechanisms by anticipating the impacts of mutations to the virus. To look at the possibility of an increased effect on the resistance phenotype of a combination of framework mutations, known to confer resistance to oseltamivir or zanamivir, with limited effect on virus fitness, we constructed 4 viruses by reverse genetics in the A/Moscow/10/99 H3N2 background containing double mutations in their neuraminidase genes: E119D؉I222L, E119V؉I222L, D198N؉I222L, and H274Y؉I222L (N2 numbering). Among the viruses produced, the E119D؉I222L mutant virus was not able to grow without bacterial NA complementation and the D198N؉I222L mutant and H274Y؉I222L mutant were not stable after passages in MDCK cells. The E119V؉I222L mutant was stable after five passages in MDCK cells. This E119V-and-I222L combination had a combinatorial effect on oseltamivir resistance. The total NA activity of the E119V؉I222L mutant was low (5% compared to that of the wild-type virus). This drop in NA activity resulted from a decreased NA quantity in the virion in comparison to that of the wild-type virus (1.4% of that of the wild type). In MDCK-SIAT1 cells, the E119V؉I222L mutant virus did not present a replicative advantage over the wild-type virus, even in the presence of oseltamivir. Double mutations combining two framework mutations in the NA gene still have to be monitored, as they could induce a high level of resistance to NIs, without impairing the NA affinity. Our study allows a better understanding of the diversity of the mechanisms of resistance to NIs.The influenza A virus presents two major surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA). HA mediates virus entry into the cell by binding to terminal sialic acid (N-acetyl neuraminic acid) of cellular glycoconjugates (52). NA, through its sialidase activity, facilitates the elution of progeny virions from infected cells through the cleavage of terminal sialic acid from viral and cellular glycoconjugates (36,44,45).Among the nine NA subtypes described, the crystal structures of the N9 (5, 57), N2 (58, 59), N6, and N1/N4/N8 subtypes (51) have been resolved. The NA head is a tetramer composed of four identical subunits arranged with a circular 4-fold symmetry. Each monomer contains six beta sheets composed of 4 antiparallel strands. The NA active site is located centrally on each unit and forms a pocket composed of conserved residues found in all influenza A virus NA (16). All these residues form the wall of the catalytic pocket. It includes catalytic sites (R118, D151, R152, R224, E276, R292, R371, and Y406) that interact directly with the substrate, sialic acid, and framework sites (E119, R156, W178, S179, D/N198, I222, E227, H274, E277, N294, and E425) that interact with catalytic residues to stabilize the active site (15).Due to its conserved structure and its essential role in viral replication, NA is an attractive antiviral t...

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“…Therefore, stockpiling of this antiviral has been included in pandemic preparedness plans [Oxford, 2007]. There have been efforts to monitor emergence of oseltamivir resistant strains of influenza viruses, and relatively low rates of resistance were reported until the last quarter of 2007 [McKimm-Breschkin et al, 2003;Mungall et al, 2004;Ferraris et al, 2005;Monto et al, 2006;Escuret et al, 2008] This study, conducted by one of the two National Influenza Reference Laboratories in Turkey, aimed to investigate the rate and distribution of influenza types and sub-types during 2007-2008 season in Turkey, and to determine the oseltamivir resistance in A/H1N1 isolates during the season. In this study, N1 numbering was used when sequencing results of the N1 gene segment was analyzed for resistance (http://www.…”

Section: Introductionmentioning

confidence: 99%

Surveillance and oseltamivir resistance of human influenza a virus in Turkey during the 2007–2008 season

Cıblak

Hasöksüz

Escuret

et al. 2009

Journal of Medical Virology

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Monitoring the activity of influenza viruses is important for establishing the circulating types and for detection of the emergence of novel sub-types and antiviral resistant strains. This is the first report from Turkey on the surveillance and oseltamivir resistance of influenza viruses in 2007-2008. Five hundred twenty-four nasal swabs were tested from different geographical regions in Turkey during November 2007-April 2008. One hundred sixty-three (31%) samples were positive for influenza viruses of which 111 (68%) were influenza A, 52 (31%) influenza B using an immuno-capture ELISA. Forty isolates were selected at random from influenza A positive samples and grown in MDCK cell cultures. The supernatant of the cell cultures was used for RNA extraction followed by RT-PCR to detect the sub-types. Sub-typing revealed all samples as A/H1N1. The N1 gene segment of 30 A/H1N1 samples was sequenced in part, from the 201st to 365th residue, which included the critical region for oseltamivir resistance. Then resulting sequences were analyzed with oseltamivir sensitive and resistant strains obtained from National Center for Biotechnology Information (NCBI) GenBank by CLC Main Workbench Software. H275Y (H274Y according to N2 numbering) mutation, which is known to confer resistance to oseltamivir, was detected in 6 out of 30 (20%) H1N1 isolates from four cities (Istanbul, Bursa, Ankara, and Izmir). The D354G mutation was observed in all oseltamivir resistant H1N1 isolates but not in the oseltamivir sensitive isolates. Assay of neuraminidase activity revealed that these isolates were resistant to oseltamivir, but sensitive to zanamivir.

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Sensitivity of influenza viruses to zanamivir and oseltamivir: A study performed on viruses circulating in France prior to the introduction of neuraminidase inhibitors in clinical practice

Cited by 75 publications

References 30 publications

Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype

Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype

Combinatorial Effect of Two Framework Mutations (E119V and I222L) in the Neuraminidase Active Site of H3N2 Influenza Virus on Resistance to Oseltamivir

Surveillance and oseltamivir resistance of human influenza a virus in Turkey during the 2007–2008 season

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