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Virulence of rimantadine-resistant human influenza A (H3N2) viruses in ferrets
C Sweet1, F G Hayden, K J Jakeman
1Microbial Molecular Genetics and Cell Biology Research Group, University of Birmingham, United Kingdom.
Abstract:
The influence of rimantadine-resistance mutations on the virulence of human H3N2 viruses in ferrets was examined. The similarities in virulence of the drug-resistant mutants with single amino acid substitutions at three different locations, 27, 30, and 31, within the M2 sequence and their corresponding sensitive wild-type isolates contrasted with differences in virulence between the three pairs of viruses. These data provide further evidence that rimantadine-resistant viruses that emerge during treatment of patients with the drug are unaltered both in their growth characteristics and virulence.
Insights
Rimantadine-resistance mutations in H3N2 influenza viruses did not alter virulence in ferrets. Emergent drug-resistant viruses maintain similar growth and virulence, suggesting no fitness cost.
Area of Science:
- Virology
- Infectious Diseases
- Drug Resistance
Background:
- Influenza H3N2 viruses can develop resistance to antiviral drugs like rimantadine.
- Understanding the impact of resistance mutations on viral fitness is crucial for treatment strategies.
Purpose of the Study:
- To investigate the influence of rimantadine-resistance mutations on the virulence of human H3N2 influenza viruses in a ferret model.
- To compare the virulence of drug-resistant mutants with their sensitive wild-type counterparts.
Main Methods:
- Generation of H3N2 influenza virus mutants with single amino acid substitutions in the M2 protein.
- Assessment of viral virulence and growth characteristics in a ferret model.
- Comparative analysis of drug-resistant and drug-sensitive virus pairs.
Main Results:
- Rimantadine-resistant H3N2 virus mutants with single amino acid substitutions at positions 27, 30, and 31 in the M2 sequence showed similar virulence to their wild-type counterparts.
- While some differences in virulence were observed between specific mutant-wild-type pairs, overall virulence was largely unaffected.
- Emergence of rimantadine resistance during treatment did not compromise viral growth or virulence.
Conclusions:
- Rimantadine-resistance mutations in H3N2 influenza viruses do not significantly impact viral virulence in ferrets.
- Viruses that develop resistance during antiviral therapy retain their growth characteristics and virulence, indicating no significant fitness penalty.