Evaluation of pathogenic characteristics in animal models infected with influenza A and B viruses
10.13200/j.cnki.cjb.004657
- VernacularTitle:A和B型流感病毒感染动物模型致病特征的评价
- Author:
Cailing DAI
1
Author Information
1. Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd., Guangdong Provincial Key Laboratory of Drug Non⁃Clinical Evaluation and Research, TCM Non⁃clinic Evaluation Branch of National Engineering Research Center for Modernization of Traditional Chinese Medicine, Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Conghua District Anti⁃infective Drug Research and Evaluation Engineering Technology Research Center, Guangzhou 510990, Guangdong Province, China
- Publication Type:Journal Article
- Keywords:
Influenza virus;
Infection model;
Pathogenic characteristics;
Viral load;
Histopathology
- From:
Chinese Journal of Biologicals
2026;39(02):144-151+161
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish influenza A and influenza B virus infection models in mice, systematically evaluate the pathogenic characteristics of different strains in vivo, so as to provide experimental tools for vaccine immunogenicity assessment and antiviral drug screening.Methods SPF-grade BALB/c mice were intranasally inoculated with gradient viral doses of seasonal epidemic virus strains A/H3N2, A/H1N1, B/Vic, and B/Yam circulating in the Northern Hemisphere 2021-2022.The body mass changes, mortality, and clinical symptoms were dynamically monitored for 7 days. Animals were euthanized on days 4 and 7 post-infection. Five lung lobes(left and right) were dissected for viral load quantification by qPCR and histopathological examination to determine the optimal modeling infection dose of each strain. The optimal dose was used for verification test, and the viral loads, pathological changes and inflammatory cytokine levels were measured 7 days after infection.Results Two days after infection with A/H1N1, B/Vic, and B/Yam strains, the body mass of mice began to decrease, and the viral loads in lung tissues reached the peak on the 4 th day after infection, accompanied by moderate interstitial pneumonia characterized by fibrinous exudates in alveolar spaces and inflammatory cell infiltration. The viral loads persisted until day 7 without decline after infection, and the pathological damage persisted. The viral load and pathological changes in different parts of the lung tissue of the same mouse were different, and individual differences were large. No significant body mass fluctuations were observed across all dose groups of A/H3N2 strain, the pulmonary viral loads remained below detection thresholds,and histopathology revealed no influenza-specific lesions, indicating inefficient replication in BALB/c mice. The optimal modeling infection doses of A/H1N1, B/Vic, and B/Yam strains were determined to be 1. 6 × 10~5, 8. 9 × 10~2, and 2. 5 × 10~4 TCID_(50),respectively. Verification experiments showed that 7 days after infection with A/H1N1, B/Vic, and B/Yam strains, mice all experienced body mass loss and corresponding clinical symptoms, and the viral loads in lung tissues were all more than6 lgcopies/??g RNA. Typical pathological changes of interstitial pneumonia were observed, accompanied by increased levels of key inflammatory cytokines such as TNF-α, IL-6, and IFNγ.Conclusion A/H1N1, B/Vic and B/Yam strains can establish stable infection models in BALB/c mice, which are suitable for vaccine efficacy assessments and preliminary drug screening. A/H3N2 strain has not been effectively replicated in mice, and ferret model can be used for related research.
