PandemieGrippaleV1, Main, Exploration, bibRecord, 001851

Evaluation of Recombinant 2009 Pandemic Influenza A (H1N1) Viruses Harboring Zanamivir Resistance Mutations in Mice and Ferrets

Identifieur interne : 001851 ( Main/Exploration ); précédent : 001850; suivant : 001852

Evaluation of Recombinant 2009 Pandemic Influenza A (H1N1) Viruses Harboring Zanamivir Resistance Mutations in Mice and Ferrets

Auteurs : Andres Pizzorno [Canada] ; Yacine Abed [Canada] ; Chantal Rheaume [Canada] ; Xavier Bouhy [Canada] ; Guy Boivin [Canada]

Source :

Antimicrobial agents and chemotherapy [ 0066-4804 ] ; 2013.

RBID : Pascal:13-0150859

Descripteurs français

Pascal (Inist)
- Evaluation, Protéine recombinante, Virus grippal A, Zanamivir, Résistance, Mutation, Génétique, Animal, Souris, Furet, Antiviral, Grippe pandémique, Grippe H1N1, Virus grippal A(H1N1).
Wicri :
- topic : Génétique.

English descriptors

KwdEn :
- Animal, Antiviral, Evaluation, Ferret, Genetics, H1N1 influenza, Influenza A (H1N1), Influenza A virus, Mouse, Mutation, Recombinant protein, Resistance, Zanamivir.

Abstract

Recombinant influenza A(H1N1)pdm09 wild-type (WT) and zanamivir-resistant E119G and Q136K neuraminidase mutants were generated to determine their enzymatic and replicative properties in vitro, as well as their infectivity and transmissibility in mice and ferrets. Viral titers of recombinant E119G and Q136K mutants were significantly lower than those of the WT in the first 36 h postinoculation (p.i.) in vitro. The E119G and Q136K mutations were both associated with a significant reduction of total neuraminidase (NA) activity at the cell surface of 293T cells, with relative total NA activities of 14% (P < 0.01) and 20% (P < 0.01), respectively, compared to the WT. The E119G mutation significantly reduced the affinity (8-fold increase in K_m) but not the V_max. The Q136K mutation increased the affinity (5-fold decrease in K_m) with a reduction in V_max (8% V_max ratio versus the WT). In mice, infection with the E119G and Q136K mutants resulted in lung viral titers that were significantly lower than those of the WT on days 3 p.i. (3.4 × 10⁶ ± 0.8 × 10⁶ and 2.1 × 10⁷ ± 0.4 × 10⁷ PFU/ml, respectively, versus 8.8 × 10⁷ ± 1.1 × 10⁷; P < 0.05) and 6 p.i. (3.0 × 10⁵ ± 0.5 × 10⁵ and 8.6 × 10⁵ ± 1.4 × 10⁵ PFU/ml, respectively, versus 5.8 × 10⁷ ± 0.3 × 10⁷ ; P < 0.01). In experimentally infected ferrets, the E119G mutation rapidly reverted to the WT in donor and contact animals. The Q136K mutation was maintained in ferrets, although nasal wash viral titers from the Q136K contact group were significantly lower than those of the WT on days 3 to 5 p.i. Our results demonstrate that zanamivir-resistant E119G and Q136K mutations compromise viral fitness and transmissibility in A(H1N1)pdm09 viruses.

Affiliations:

Canada

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Le document en format XML

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<front><div type="abstract" xml:lang="en">Recombinant influenza A(H1N1)pdm09 wild-type (WT) and zanamivir-resistant E119G and Q136K neuraminidase mutants were generated to determine their enzymatic and replicative properties in vitro, as well as their infectivity and transmissibility in mice and ferrets. Viral titers of recombinant E119G and Q136K mutants were significantly lower than those of the WT in the first 36 h postinoculation (p.i.) in vitro. The E119G and Q136K mutations were both associated with a significant reduction of total neuraminidase (NA) activity at the cell surface of 293T cells, with relative total NA activities of 14% (P < 0.01) and 20% (P < 0.01), respectively, compared to the WT. The E119G mutation significantly reduced the affinity (8-fold increase in K<sub>m</sub>
) but not the V<sub>max</sub>
. The Q136K mutation increased the affinity (5-fold decrease in K<sub>m</sub>
) with a reduction in V<sub>max</sub>
 (8% V<sub>max</sub>
 ratio versus the WT). In mice, infection with the E119G and Q136K mutants resulted in lung viral titers that were significantly lower than those of the WT on days 3 p.i. (3.4 × 10<sup>6</sup>
 ± 0.8 × 10<sup>6</sup>
 and 2.1 × 10<sup>7</sup>
 ± 0.4 × 10<sup>7</sup>
 PFU/ml, respectively, versus 8.8 × 10<sup>7</sup>
 ± 1.1 × 10<sup>7</sup>
; P < 0.05) and 6 p.i. (3.0 × 10<sup>5</sup>
 ± 0.5 × 10<sup>5</sup>
 and 8.6 × 10<sup>5</sup>
 ± 1.4 × 10<sup>5</sup>
 PFU/ml, respectively, versus 5.8 × 10<sup>7</sup>
 ± 0.3 × 10<sup>7</sup>
 ; P < 0.01). In experimentally infected ferrets, the E119G mutation rapidly reverted to the WT in donor and contact animals. The Q136K mutation was maintained in ferrets, although nasal wash viral titers from the Q136K contact group were significantly lower than those of the WT on days 3 to 5 p.i. Our results demonstrate that zanamivir-resistant E119G and Q136K mutations compromise viral fitness and transmissibility in A(H1N1)pdm09 viruses.</div>
</front>
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<tree><country name="Canada"><noRegion><name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andres" last="Pizzorno">Andres Pizzorno</name>
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<name sortKey="Abed, Yacine" sort="Abed, Yacine" uniqKey="Abed Y" first="Yacine" last="Abed">Yacine Abed</name>
<name sortKey="Boivin, Guy" sort="Boivin, Guy" uniqKey="Boivin G" first="Guy" last="Boivin">Guy Boivin</name>
<name sortKey="Bouhy, Xavier" sort="Bouhy, Xavier" uniqKey="Bouhy X" first="Xavier" last="Bouhy">Xavier Bouhy</name>
<name sortKey="Rheaume, Chantal" sort="Rheaume, Chantal" uniqKey="Rheaume C" first="Chantal" last="Rheaume">Chantal Rheaume</name>
</country>
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Evaluation of Recombinant 2009 Pandemic Influenza A (H1N1) Viruses Harboring Zanamivir Resistance Mutations in Mice and Ferrets

Evaluation of Recombinant 2009 Pandemic Influenza A (H1N1) Viruses Harboring Zanamivir Resistance Mutations in Mice and Ferrets

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri