Increase of permissive secondary antiviral mutations in the evolution of A(H1N1)pdm09 influenza virus neuraminidases
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
The unexpected emergence of oseltamivir-resistant A(H1N1) viruses in 2008 was facilitated in part by the establishment of permissive secondary neuraminidase (NA) substitutions that compensated for the fitness loss due to the NA-H275Y resistance substitution. These viruses were replaced in 2009 by oseltamivir-susceptible A(H1N1)pdm09 influenza viruses.
Methods
Genetic analysis and screening A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2024 were conducted to identify any potentially permissive or resistance-associated NA substitutions. Selected viruses were then subjected to further characterization in vitro.
Results
In the NA gene of circulating A(H1N1)pdm09 viruses, two secondary permissive substitutions, NA-V241I and NA-N369K, were identified. These substitutions demonstrated a stable lineage in phylogenetic analysis since the 2010-2011 influenza season. The data indicates a slight increase in viral NA bearing two additional potentially permissive substitutions, NA-I223V and NA-S247N, in the 2023-2024 season, that both result in a slight reduction in susceptibility to NA inhibitors.
Conclusions
The accumulation of secondary permissive substitutions in the NA of A(H1N1)pdm09 viruses increases the probability of the emergence of antiviral-resistant viruses. Therefore, it is crucial to closely monitor the evolution of circulating influenza viruses and to develop additional antiviral drugs against different target proteins.
