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A reverse genetics study of resistance to neuraminidase inhibitors in an influenza A/H1N1 virus.

Abstract

A system of reverse genetics was used to generate influenza A/H1N1 viruses harbouring neuraminidase (NA) mutations previously associated with resistance to NA inhibitors in various viral subtypes. The His274Tyr and Glu119Gln mutants were rescued whereas the Arg292Lys and Glu1l9 --> Gly, Val, Ala or Asp mutants could not be generated. In NA inhibition assays, the His274Tyr mutant was resistant to oseltamivir (430-fold over wild-type) and BCX-1812 (50-fold) but was sensitive to zanamivir. A similar trend was seen when the mutant was evaluated by plaque reduction assay (PRA). The Glu119Gln mutant expressed a low level of resistance to oseltamivir (nine-fold) and zanamivir (fourfold) in NA inhibition assay but was only marginally resistant to oseltamivir (fourfold) in PRA. The replication capacity of both mutants, in particular that of the His274Tyr virus, was impaired when compared with the wild-type virus in vitro.

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Authors+Show Affiliations

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Research Center in Infectious Diseases of the CHUQ-CHUL, Québec City, Canada.

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Source

Antiviral therapy 9:4 2004 Aug pg 577-81

MeSH

Acetamides
Antiviral Agents
Cyclopentanes
Drug Resistance, Viral
Enzyme Inhibitors
Guanidines
Humans
Influenza A Virus, H1N1 Subtype
Influenza A virus
Inhibitory Concentration 50
Mutation
Neuraminidase
Oseltamivir
Pyrans
Recombination, Genetic
Sialic Acids
Zanamivir

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15456089

Citation

Abed, Yacine, et al. "A Reverse Genetics Study of Resistance to Neuraminidase Inhibitors in an Influenza A/H1N1 Virus." Antiviral Therapy, vol. 9, no. 4, 2004, pp. 577-81.
Abed Y, Goyette N, Boivin G. A reverse genetics study of resistance to neuraminidase inhibitors in an influenza A/H1N1 virus. Antivir Ther (Lond). 2004;9(4):577-81.
Abed, Y., Goyette, N., & Boivin, G. (2004). A reverse genetics study of resistance to neuraminidase inhibitors in an influenza A/H1N1 virus. Antiviral Therapy, 9(4), pp. 577-81.
Abed Y, Goyette N, Boivin G. A Reverse Genetics Study of Resistance to Neuraminidase Inhibitors in an Influenza A/H1N1 Virus. Antivir Ther (Lond). 2004;9(4):577-81. PubMed PMID: 15456089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A reverse genetics study of resistance to neuraminidase inhibitors in an influenza A/H1N1 virus. AU - Abed,Yacine, AU - Goyette,Nathalie, AU - Boivin,Guy, PY - 2004/10/1/pubmed PY - 2005/4/7/medline PY - 2004/10/1/entrez SP - 577 EP - 81 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 9 IS - 4 N2 - A system of reverse genetics was used to generate influenza A/H1N1 viruses harbouring neuraminidase (NA) mutations previously associated with resistance to NA inhibitors in various viral subtypes. The His274Tyr and Glu119Gln mutants were rescued whereas the Arg292Lys and Glu1l9 --> Gly, Val, Ala or Asp mutants could not be generated. In NA inhibition assays, the His274Tyr mutant was resistant to oseltamivir (430-fold over wild-type) and BCX-1812 (50-fold) but was sensitive to zanamivir. A similar trend was seen when the mutant was evaluated by plaque reduction assay (PRA). The Glu119Gln mutant expressed a low level of resistance to oseltamivir (nine-fold) and zanamivir (fourfold) in NA inhibition assay but was only marginally resistant to oseltamivir (fourfold) in PRA. The replication capacity of both mutants, in particular that of the His274Tyr virus, was impaired when compared with the wild-type virus in vitro. SN - 1359-6535 UR - https://www.unboundmedicine.com/medline/citation/15456089/A_reverse_genetics_study_of_resistance_to_neuraminidase_inhibitors_in_an_influenza_A/H1N1_virus_ DB - PRIME DP - Unbound Medicine ER -