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Updated: Sep 16, 2025
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Dynamic adaptation mutations and pathogenic characterization of a mouse-adapted seasonal human H3N2 influenza virus
Cheng Zhang1,2, Yan Li2, Ning Zhang2
1College of Life Science and Technology, Xinjiang University, Urumchi, 830046, China.
Background:
H3N2 influenza A viruses [A(H3N2)] circulate as seasonal influenza in humans worldwide, resulting in a huge disease burden. Adaptation study of A(H3N2) in mice could provide a basis for preclinical evaluation of antivirals and vaccines targeting A(H3N2) and identify the genetic markers responsible for the viral adaptation, replication, and pathogenesis.
Methods:
Lung-to-lung passaging of wild-type (WT) A(H3N2) strain was performed in C57BL/6J mice. Amino acid (AA) mutations occurred during the passaging and temporal dynamics of these mutations were identified using the next-generation sequencing. We determined the polymerase activity of the ribonucleoprotein (RNP) complex containing mutation genes and compared the pathogenicity between the mouse-adapted (MA) and A(H3N2)-WT strains based on body weight change, survival rate, lung index, lung viral load, and lung pathology of the infected mice.
Results:
The A(H3N2)-MA strain was obtained after seventeen lung-to-lung passages in mice. 14 AA mutations in the PB2, PB1, PA, HA, NP, and M1 genes were identified in the A(H3N2)-MA strain compared to the A(H3N2)-WT strain. In addition, the polymerase activity of the RNP complex containing mutation genes was increased, and the pathogenicity of the MA virus is significantly higher than that of the WT strain.
Conclusions:
One A(H3N2)-MA strain has been developed that can infect and kill mice. The MA strain showed stronger replication ability and pathogenicity than the A(H3N2)-WT strain. This A(H3N2)-MA model provides a valuable basis for evaluating the effects of drugs and vaccines and for studying pathogenesis.
Insights
A mouse-adapted H3N2 influenza virus was developed through serial passaging. This adapted strain exhibits enhanced replication and pathogenicity, offering a valuable model for antiviral and vaccine research.
Area of Science:
- Virology
- Infectious Diseases
- Immunology
Background:
- Influenza A virus subtype H3N2 (A(H3N2)) causes significant global disease burden.
- Adapting A(H3N2) in mice is crucial for preclinical evaluation of therapeutics and understanding viral adaptation.
Purpose of the Study:
- To develop a mouse-adapted A(H3N2) strain for preclinical studies.
- To identify genetic markers associated with A(H3N2) adaptation, replication, and pathogenesis in mice.
Main Methods:
- Serial lung-to-lung passaging of wild-type A(H3N2) in C57BL/6J mice.
- Next-generation sequencing to identify amino acid mutations.
- Assessment of viral pathogenicity through body weight changes, survival rates, lung viral load, and pathology.
Main Results:
- A mouse-adapted A(H3N2) strain (A(H3N2)-MA) was generated after 17 passages.
- 14 amino acid mutations were identified in key viral genes (PB2, PB1, PA, HA, NP, M1).
- The A(H3N2)-MA strain demonstrated increased polymerase activity and significantly higher pathogenicity compared to the wild-type strain.
Conclusions:
- A novel mouse-adapted A(H3N2) strain capable of infecting and causing mortality in mice has been established.
- This A(H3N2)-MA model exhibits enhanced replication and pathogenicity, serving as a valuable tool for drug and vaccine efficacy testing and pathogenesis research.
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