Amantadine resistance in clinical influenza A (H3N2) and (H1N1) virus isolates
Abstract:
Thirty-nine influenza A (H1N1) and (H3N2) virus isolates were examined for their susceptibility to amantadine in allantois-on-shell (AOS) cultures. A range of susceptibilities was found when isolates were titrated in the presence of 2.5 mg/l amantadine. Further titration of resistant isolates at 25 mg/l revealed one isolate which remained totally resistant at this higher concentration. A series of cloned viruses was derived from this resistant isolate, and one other partially resistant isolate, by limiting dilution AOS passage in the absence of amantadine. When these were titrated in the presence of 25 mg/l amantadine, a heterogeneity of amantadine-resistance phenotypes was observed in both sets of virus clones. Finally, chronological ordering of clinical isolates and reference strains tested in this study suggests a higher incidence of amantadine resistance amongst more recent influenza A virus isolates.
Insights
Influenza A virus isolates show varying susceptibility to amantadine antiviral medication. More recent influenza A strains exhibit a higher incidence of amantadine resistance, impacting treatment options.
Area of Science:
- Virology
- Antimicrobial Resistance
Background:
- Influenza A viruses are a significant cause of seasonal epidemics and occasional pandemics.
- Amantadine is an antiviral drug historically used for influenza A treatment and prophylaxis.
- Emergence of antiviral resistance can limit the effectiveness of influenza therapies.
Purpose of the Study:
- To assess the susceptibility of contemporary influenza A virus isolates to amantadine.
- To investigate the genetic basis and phenotypic characteristics of amantadine resistance in influenza A viruses.
Main Methods:
- Susceptibility testing of 39 influenza A (H1N1 and H3N2) isolates using allantois-on-shell (AOS) cultures.
- Titration of isolates in the presence of varying amantadine concentrations (2.5 mg/l and 25 mg/l).
- Derivation and characterization of cloned viruses from resistant isolates via limiting dilution passage.
Main Results:
- A spectrum of amantadine susceptibility was observed among the influenza A isolates.
- One isolate demonstrated complete resistance at 25 mg/l amantadine.
- Cloned viruses derived from resistant isolates displayed heterogeneous amantadine resistance phenotypes.
- A trend towards increased amantadine resistance in more recent influenza A virus isolates was noted.
Conclusions:
- Contemporary influenza A virus isolates exhibit varying levels of amantadine resistance.
- The study identified heterogeneity in amantadine resistance phenotypes within virus clones.
- Increasing amantadine resistance in recent influenza A strains may necessitate alternative antiviral strategies.
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