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Updated: Sep 23, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Kinetic profile of influenza virus infection in three rat strains
Mary J Daniels1, MaryJane K Selgrade, Donald Doerfler
1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711, USA.
Abstract:
Influenza is a respiratory tract disease of viral origin that can cause major epidemics in humans. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembles those seen in humans with influenza, and can result in severe and even fatal pneumonia. In contrast, experimental infection of rats with the virus induces a milder form of the disease, with no mortality. The purpose of the study reported here was to determine the time course of influenza infection and lung injury in Brown Norway (BN), Fischer-344 (F344), and Sprague-Dawley (SD) rats to ascertain whether genetic background impacts susceptibility to infection and host responses. Rats of each strain were inoculated intranasally with 10,000 plaque-forming units of rat-adapted influenza virus (RAIV), and lungs were assessed at postinoculation hour (PIH) 2, 24, 48, 72, and 144 for viral titer, inflammatory cells, pro-inflammatory cytokines, and biochemical indicators of lung edema (protein) and injury (lactate dehydrogenase [LD] activity). Virus titer peaked at PIH 24, and was 100-fold higher in the F344 and SD, compared with the BN strain. Alveolar macrophages, LD activity, and total protein concentration were higher in the BN rats, whereas neutrophil numbers and interleukin 6 and tumor necrosis factor-alpha activities were greatest in the bronchoalveolar lavage fluid of F344 and SD rats. The results indicate that F344 and SD rats respond in similar manner to viral infection, whereas viral replication was more limited in BN rats and was associated with a different profile of pulmonary cells.
Insights
Genetic background impacts influenza virus infection in rats. Fischer-344 and Sprague-Dawley rats showed higher viral loads and inflammation, while Brown Norway rats had limited viral replication and different immune cell responses.
Area of Science:
- Virology
- Immunology
- Respiratory Medicine
Background:
- Influenza virus causes respiratory illness and pneumonia in humans and mice.
- Rat models of influenza infection exhibit milder disease compared to mice.
- Genetic factors may influence influenza susceptibility and host response.
Purpose of the Study:
- To investigate the time course of influenza infection and lung injury in three rat strains: Brown Norway (BN), Fischer-344 (F344), and Sprague-Dawley (SD).
- To determine if the genetic background of rats affects their susceptibility to influenza virus and their host immune responses.
Main Methods:
- Rats of BN, F344, and SD strains were intranasally inoculated with rat-adapted influenza virus (RAIV).
- Lungs were assessed at various time points (2, 24, 48, 72, 144 hours postinoculation) for viral titer, inflammatory cells, cytokines, and indicators of lung injury.
- Measurements included viral load, lactate dehydrogenase (LD) activity, protein concentration, and levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α).
Main Results:
- Viral titer peaked at 24 hours postinoculation, being 100-fold higher in F344 and SD rats compared to BN rats.
- BN rats showed higher levels of alveolar macrophages, LD activity, and total protein, indicating distinct lung injury patterns.
- F344 and SD rats exhibited greater neutrophil numbers and higher IL-6 and TNF-α activity in bronchoalveolar lavage fluid.
Conclusions:
- Fischer-344 and Sprague-Dawley rats demonstrate similar responses to influenza virus infection.
- Brown Norway rats exhibit more limited viral replication and a different pulmonary cellular response profile.
- Rat genetic background significantly influences influenza virus infection dynamics and host-pathogen interactions.
