التفاصيل البيبلوغرافية
| العنوان: |
Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases. |
| المؤلفون: |
Duwe, Susanne C.1 (AUTHOR) duwes@rki.de, Milde, Jeanette1 (AUTHOR), Heider, Alla1 (AUTHOR), Wedde, Marianne1 (AUTHOR), Schweiger, Brunhilde1 (AUTHOR), Dürrwald, Ralf1 (AUTHOR) |
| المصدر: |
Viruses (1999-4915). Jul2024, Vol. 16 Issue 7, p1109. 11p. |
| مصطلحات موضوعية: |
*INFLUENZA viruses, *GENETIC testing, *NEURAMINIDASE, *ANTIVIRAL agents, *INFLUENZA |
| مستخلص: |
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. Genetic analysis and screening of A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2024 were conducted to identify any potentially synergistic or resistance-associated NA substitutions. Selected viruses were then subjected to further characterization in vitro. In the NA gene of circulating A(H1N1)pdm09 viruses, two secondary 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 indicate a slight increase in viral NA bearing two additional potentially synergistic substitutions, NA-I223V and NA-S247N, in the 2023–2024 season, which both result in a slight reduction in susceptibility to NA inhibitors. The accumulation of secondary synergistic 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. [ABSTRACT FROM AUTHOR] |
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