title: Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies.
abstract: Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours ('Color-flu' viruses) to facilitate the study of viral infection in in vivo models. On adaptation to mice, stable expression of the fluorescent proteins in infected animals allows their detection by different types of microscopy and by flow cytometry. We use this system to analyse the progression of viral spread in mouse lungs, for live imaging of virus-infected cells, and for differential gene expression studies in virus antigen-positive and virus antigen-negative live cells in the lungs of Color-flu-infected mice. Collectively, Color-flu viruses are powerful tools to analyse virus infections at the cellular level in vivo to better understand influenza pathogenesis.
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Satoshi
authors: S
authors: Fukuyama
authors: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Hiroaki
authors: H
authors: Katsura
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Dongming
authors: D
authors: Zhao
authors: 1] Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan [2] Transboundary Animal Distance Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan.
authors: Makoto
authors: M
authors: Ozawa
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Tomomi
authors: T
authors: Ando
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Jason E
authors: JE
authors: Shoemaker
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Izumi
authors: I
authors: Ishikawa
authors: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Shinya
authors: S
authors: Yamada
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
authors: Gabriele
authors: G
authors: Neumann
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] Laboratory of Veterinary Microbiology, Department of Veterinary Sciences, University of Miyazaki, Miyazaki 889-2192, Japan.
authors: Shinji
authors: S
authors: Watanabe
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] The Systems Biology Institute, Minato-ku, Tokyo 108-0071, Japan [3] Sony Computer Science Laboratories, Shinagawa-ku, Tokyo 141-0022, Japan [4] Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan.
authors: Hiroaki
authors: H
authors: Kitano
authors: 1] Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan [2] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan [3] Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA [4] Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors: Yoshihiro
authors: Y
authors: Kawaoka
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000235:genetics*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics*; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics*; D008168:Lung / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014779:Virus Replication; D000097573:Red Fluorescent Protein
chemical_list: D001426:Bacterial Proteins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D017361:Viral Nonstructural Proteins; D000097573:Red Fluorescent Protein; C085820:INS1 protein, influenza virus; C054562:yellow fluorescent protein, Bacteria