In vivo imaging of the pathophysiological changes and neutrophil dynamics in influenza virus-infected mouse lungs

The pathophysiological changes that occur in lungs infected with influenza viruses are poorly understood. Here we established an in vivo imaging system that combines two-photon excitation microscopy and fluorescent influenza viruses of different pathogenicity. This approach allowed us to monitor and...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 115; no. 28; pp. E6622 - E6629
Main Authors Ueki, Hiroshi, Wang, I-Hsuan, Fukuyama, Satoshi, Katsura, Hiroaki, da Silva Lopes, Tiago Jose, Neumann, Gabriele, Kawaoka, Yoshihiro
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 10.07.2018
SeriesPNAS Plus
Subjects
Animals
Biological Sciences
Fluorescence
Histopathology
Imaging
Influenza
Influenza A Virus, H5N1 Subtype - genetics
Influenza A Virus, H5N1 Subtype - metabolism
Information systems
Leukocytes (neutrophilic)
Lung - metabolism
Lung - pathology
Lung - virology
Lung diseases
Lungs
Mice
Microscopy, Fluorescence, Multiphoton
Neutrophils
Orthomyxoviridae
Orthomyxoviridae Infections - genetics
Orthomyxoviridae Infections - metabolism
Orthomyxoviridae Infections - pathology
Pathogenicity
Pathogens
Perfusion
Permeability
Physiology
PNAS Plus
Viruses
lung
influenza virus
in vivo imaging
neutrophil dynamics
two-photon excitation microscopy
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Summary:The pathophysiological changes that occur in lungs infected with influenza viruses are poorly understood. Here we established an in vivo imaging system that combines two-photon excitation microscopy and fluorescent influenza viruses of different pathogenicity. This approach allowed us to monitor and correlate several parameters and physiological changes including the spread of infection, pulmonary permeability, pulmonary perfusion speed, number of recruited neutrophils in infected lungs, and neutrophil motion in the lungs of live mice. Several physiological changes were larger and occurred earlier in mice infected with a highly pathogenic H5N1 influenza virus compared with those infected with a mouse-adapted human strain. These findings demonstrate the potential of our in vivo imaging system to provide novel information about the pathophysiological consequences of virus infections.
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Contributed by Yoshihiro Kawaoka, June 1, 2018 (sent for review April 23, 2018; reviewed by Daniel R. Perez and Stacey L. Schultz-Cherry)
Author contributions: H.U., S.F., H.K., and Y.K. designed research; H.U. and I.-H.W. performed research; H.U., I.-H.W., and T.J.d.S.L. analyzed data; H.U., I.-H.W., S.F., G.N., and Y.K. wrote the paper; and Y.K. provided overall coordination with respect to the concept, design, and supervision of the study.
Reviewers: D.R.P., University of Georgia; and S.L.S.-C., St. Jude Children’s Research Hospital.
1H.U. and I.-H.W. contributed equally to this work.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1806265115