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Updated: Mar 26, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models
E A Prokopyeva1, I A Sobolev2, M V Prokopyev3
1Novosibirsk State University, 630090 Novosibirsk, Russian Federation; Federal State Budgetary Scientific Institution "Research Institute of Experimental and Clinical Medicine", Siberian Branch of the Russian Academy of Medical Sciences, 630117 Novosibirsk, Russian Federation.
Abstract:
In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model.
Insights
Influenza A(H1N1)pdm09 virus adapted to mice showed increased virulence and caused 100% mortality. Genetic analysis revealed mutations contributing to this adaptation, but pathogenicity varied across mouse models.
Area of Science:
- Virology
- Infectious Diseases
- Genetics
Background:
- Influenza A(H1N1)pdm09 virus is a significant human pathogen.
- Mouse models are crucial for studying influenza virus pathogenesis and adaptation.
Purpose of the Study:
- To adapt influenza A(H1N1)pdm09 virus to mice through serial lung passages.
- To investigate the genetic basis of increased virulence in mouse-adapted variants.
- To assess the pathogenicity of adapted variants in different mouse strains.
Main Methods:
- Generation of mouse-adapted influenza A(H1N1)pdm09 virus variants via serial lung-to-lung passages in BALB/c, C57BL/6, and CD1 mice.
- Assessment of virulence and pathogenicity through mortality rates in adapted mice.
- Genetic analysis to identify mutations in viral proteins (PB2, PB1, HA, NP, NA, NS2).
Main Results:
- All mouse-adapted variants exhibited significantly increased virulence, leading to 100% mortality in infected mice.
- Identical amino acid substitutions were observed across all adapted variants in key viral proteins.
- Cross-challenge experiments indicated that not all adapted variants were pathogenic for different mouse strains.
Conclusions:
- Influenza A(H1N1)pdm09 virus can readily adapt to mice, acquiring mutations that enhance virulence and lethality.
- The specific mutations identified are critical for host adaptation and increased pathogenicity.
- Findings highlight the importance of considering mouse strain-specific pathogenicity when utilizing influenza mouse models for research.
