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Updated: Jun 18, 2026
Modeling Dysplastic and Functional Lung Alveolar Repair after Influenza Infection
Published on: September 19, 2025
Pulmonary fibrosis induced by H5N1 viral infection in mice
Jian Qiao1, Miaojie Zhang, Jianmin Bi
1Department of Pathophysiology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China. qiaojian@cau.edu.cn
Background:
Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus.
Methods:
Eight-week-old BALB/c mice were inoculated intranasally with 1 x 101 MID50 of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation.
Results:
H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice.
Conclusion:
Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.
Insights
H5N1 virus infection in mice causes lung injury and inflammation, leading to pulmonary fibrosis (PF) during the recovery period. This study details the fibrotic changes observed in mice following H5N1 infection.
Area of Science:
- Virology
- Pathology
- Immunology
Background:
- Inflammatory processes can cause lung injury, potentially leading to pulmonary fibrosis (PF).
- The H5N1 influenza virus is known to cause severe respiratory illness.
Purpose of the Study:
- To investigate the development of pulmonary fibrosis (PF) in a mouse model infected with the H5N1 virus.
- To characterize the pathological changes associated with H5N1-induced lung injury and fibrosis.
Main Methods:
- BALB/c mice were intranasally inoculated with H5N1 virus.
- Lung injury and fibrosis were assessed via hydroxyproline concentration, lung indexes, and histopathology at 7, 14, and 30 days post-infection.
Main Results:
- H5N1-infected mice exhibited a two-stage pulmonary disease progression.
- Acute stage (day 7) showed diffuse pneumonia with inflammation and edema.
- Restoration stage (day 30) revealed varying degrees of PF, with 18% of survivors developing severe fibrosis, confirmed by elevated hydroxyproline levels and increased lung-to-body weight ratio.
Conclusions:
- H5N1 virus infection in mice leads to pulmonary fibrosis during the restoration phase.
- These findings provide insights into H5N1-induced fibrogenesis and potential therapeutic targets for human H5N1 disease.
