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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Multiorgan distribution of human influenza A virus strains observed in a mouse model
T Fislová1, M Gocník, T Sládková
1Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05, Bratislava, Slovak Republic.
Abstract:
Multiorgan spread and pathogenesis of influenza infection with three human influenza A viruses was studied in mice. Mouse-adapted viruses A/Dunedin/4/73(H3N2), A/Mississippi/1/85(H3N2), and A/PR/8/34(H1N1) differed considerably in virulence (p.f.u./LD(50)): 79,000 p.f.u. for Dunedin, 5,000 p.f.u. for Mississippi, and 65 p.f.u. for PR/8, which qualified Dunedin as low virulent, Mississippi as intermediate, and PR/8 as highly virulent. All three viruses were detected in lungs, heart, and thymus by cultivation and RT-PCR. Moreover, vRNA of all viruses was found in liver and spleen, of Dunedin and PR/8 also in kidneys and that of Dunedin and Mississippi in blood. Only vRNA of Dunedin was demonstrated in brain. Lung damage accompanied by histopathological changes and thymus reduction were most extensive after infection with the highly virulent virus PR/8. We assume that the ability to spread to multiple organs may be a more common property of influenza viruses in mammalian hosts than previously believed.
Insights
Influenza A virus can spread to multiple organs in mice, with varying virulence. Highly virulent strains caused more extensive lung damage and thymus reduction, suggesting broader organ involvement than previously thought.
Area of Science:
- Virology
- Pathogenesis
- Immunology
Background:
- Influenza A virus is a significant human pathogen.
- Understanding influenza virus tropism and pathogenesis is crucial for disease control.
Purpose of the Study:
- To investigate the multiorgan spread and pathogenesis of three distinct human influenza A virus strains in a mouse model.
- To correlate viral virulence with organ distribution and observed pathological changes.
Main Methods:
- Mouse adaptation of influenza A viruses: A/Dunedin/4/73 (H3N2, low virulence), A/Mississippi/1/85 (H3N2, intermediate virulence), and A/PR/8/34 (H1N1, high virulence).
- Detection of viral RNA (vRNA) and infectious virus in various organs (lungs, heart, thymus, liver, spleen, kidneys, blood, brain) using cultivation and RT-PCR.
- Assessment of histopathological changes in lungs and thymus reduction.
Main Results:
- All three viruses replicated in lungs, heart, and thymus. Viral RNA was detected in the liver and spleen of all infected mice.
- Dunedin and PR/8 viruses showed vRNA in kidneys; Dunedin and Mississippi viruses were found in blood. Only Dunedin virus vRNA was detected in the brain.
- The highly virulent PR/8 strain induced the most severe lung damage and thymus atrophy, correlating with its virulence and broader organ spread.
Conclusions:
- Influenza A viruses exhibit a broader capacity for multiorgan spread in mammalian hosts than previously recognized.
- Viral virulence is associated with the extent of organ involvement and pathogenesis.
- These findings have implications for understanding influenza pathogenesis and host-pathogen interactions.

