دورية أكاديمية
أعرض في EDS

Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases.

التفاصيل البيبلوغرافية
العنوان: Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases.
المؤلفون: 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.
المصدر: Viruses [Viruses] 2024 Jul 11; Vol. 16 (7). Date of Electronic Publication: 2024 Jul 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Neuraminidase*/genetics , Influenza A Virus, H1N1 Subtype*/genetics , Influenza A Virus, H1N1 Subtype*/drug effects , Influenza A Virus, H1N1 Subtype*/enzymology , Antiviral Agents*/pharmacology , Drug Resistance, Viral*/genetics , Influenza, Human*/virology , Phylogeny* , Evolution, Molecular* , Viral Proteins*/genetics , Viral Proteins*/metabolism , Oseltamivir*/pharmacology , Mutation*, Humans ; Germany ; Amino Acid Substitution ; Animals ; Dogs
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.
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فهرسة مساهمة: Keywords: A(H1N1)pdm09; influenza viruses; monitoring; neuraminidase inhibitor; oseltamivir; permissive mutations; resistance; secondary mutations; surveillance
المشرفين على المادة: EC 3.2.1.18 (Neuraminidase)
0 (Antiviral Agents)
0 (Viral Proteins)
20O93L6F9H (Oseltamivir)
EC 3.2.1.18 (NA protein, influenza A virus)
تواريخ الأحداث: Date Created: 20240727 Date Completed: 20240728 Latest Revision: 20240729
رمز التحديث: 20240729
مُعرف محوري في PubMed: PMC11281601
DOI: 10.3390/v16071109
PMID: 39066271
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v16071109