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Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases.
Duwe, Susanne C; Milde, Jeanette; Heider, Alla; Wedde, Marianne; Schweiger, Brunhilde; Dürrwald, Ralf.
Afiliación
  • Duwe SC; Unit 17 Influenza and Other Respiratory Viruses, Department 1 Infectious Diseases, Robert Koch-Institute, 13353 Berlin, Germany.
  • Milde J; Unit 17 Influenza and Other Respiratory Viruses, Department 1 Infectious Diseases, Robert Koch-Institute, 13353 Berlin, Germany.
  • Heider A; Unit 17 Influenza and Other Respiratory Viruses, Department 1 Infectious Diseases, Robert Koch-Institute, 13353 Berlin, Germany.
  • Wedde M; Unit 17 Influenza and Other Respiratory Viruses, Department 1 Infectious Diseases, Robert Koch-Institute, 13353 Berlin, Germany.
  • Schweiger B; Unit 17 Influenza and Other Respiratory Viruses, Department 1 Infectious Diseases, Robert Koch-Institute, 13353 Berlin, Germany.
  • Dürrwald R; Unit 17 Influenza and Other Respiratory Viruses, Department 1 Infectious Diseases, Robert Koch-Institute, 13353 Berlin, Germany.
Viruses ; 16(7)2024 Jul 11.
Article en En | MEDLINE | ID: mdl-39066271
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Filogenia / Proteínas Virales / Evolución Molecular / Farmacorresistencia Viral / Gripe Humana / Subtipo H1N1 del Virus de la Influenza A / Oseltamivir / Mutación / Neuraminidasa Límite: Animals / Humans País/Región como asunto: Europa Idioma: En Revista: Viruses Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Filogenia / Proteínas Virales / Evolución Molecular / Farmacorresistencia Viral / Gripe Humana / Subtipo H1N1 del Virus de la Influenza A / Oseltamivir / Mutación / Neuraminidasa Límite: Animals / Humans País/Región como asunto: Europa Idioma: En Revista: Viruses Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza