ArticleScientific reports2019
Synergistic PA and HA mutations confer mouse adaptation of a contemporary A/H3N2 influenza virus.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Construction and Research Progress of Animal Models and Mouse Adapted Strains of Seasonal Influenza Virus.Vaccines · 2025Review
- Modification of H1N1 Influenza Luciferase Reporter Viruses Using StopGo Translation and/or Mouse-Adapted Mutations.Viruses · 2025Article
- Dynamic adaptation mutations and pathogenic characterization of a mouse-adapted seasonal human H3N2 influenza virus.Virology journal · 2025Article
- H3 hemagglutinin proteins optimized for 2018 to 2022 elicit neutralizing antibodies across panels of modern influenza A(H3N2) viruses.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Changes in the Expression of Proteins Associated with Neurodegeneration in the Brains of Mice after Infection with Influenza A Virus with Wild Type and Truncated NS1.International journal of molecular sciences · 2024Article
- TRIM21 restricts influenza A virus replication by ubiquitination-dependent degradation of M1.PLoS pathogens · 2023Article
- Associated virus-bacterial vaccine based on seasonal LAIV andVirulence · 2022Article
- Immunogenicity and effectiveness of a bivalent influenza A/H1N2 vaccine strain against seasonal human influenza A viruses in mice.Journal, genetic engineering & biotechnology · 2022Article
- Serial Passaging of Seasonal H3N2 Influenza A/Singapore/G2-31.1/2014 Virus in MDCK-SIAT1 Cells and Primary Chick Embryo Cells Generates HA D457G Mutation and Other Variants in HA, NA, PB1, PB1-F2, and NS1.International journal of molecular sciences · 2022Article
- Review
- Generation of a pdmH1N1 2018 Influenza A Reporter Virus Carrying a mCherry Fluorescent Protein in the PA Segment.Frontiers in cellular and infection microbiology · 2021Article
- Effects of Different Drug Combinations in Immunodeficient Mice Infected with an Influenza A/H3N2 Virus.Microorganisms · 2020Article
- Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses.Viruses · 2020Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The mouse is the most widely used animal model for influenza virus research. However, the susceptibility of mice to seasonal influenza virus depends on the strain of mouse and on the strain of the influenza virus. Seasonal A/H3N2 influenza viruses do not replicate well in mice and therefore they need to be adapted to this animal model. In this study, we generated a mouse-adapted A/H3N2 virus (A/Switzerland/9715293/2013 [MA-H3N2]) by serial passaging in mouse lungs that exhibited greater virulence compared to the wild-type virus (P0-H3N2). Seven mutations were found in the genome of MA-H3N2: PA(K615E), NP(G384R), NA(G320E) and HA(N122D, N144E, N246K, and A304T). Using reverse genetics, two synergistically acting genes were found as determinants of the pathogenicity in mice. First, the HA substitutions were shown to enhanced viral replication in vitro and, second, the PA-K615E substitution increased polymerase activity, although did not alter virus replication in vitro or in mice. Notably, single mutations had only limited effects on virulence in vitro. In conclusion, a co-contribution of HA and PA mutations resulted in a lethal mouse model of seasonal A/H3N2 virus. Such adapted virus is an excellent tool for evaluation of novel drugs or vaccines and for study of influenza pathogenesis.
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