title: In vivo bioluminescent imaging of influenza a virus infection and characterization of novel cross-protective monoclonal antibodies.
abstract: Influenza A virus is a major human pathogen responsible for seasonal epidemics as well as pandemic outbreaks. Due to the continuing burden on human health, the need for new tools to study influenza virus pathogenesis as well as to evaluate new therapeutics is paramount. We report the development of a stable, replication-competent luciferase reporter influenza A virus that can be used for in vivo imaging of viral replication. This imaging is noninvasive and allows for the longitudinal monitoring of infection in living animals. We used this tool to characterize novel monoclonal antibodies that bind the conserved stalk domain of the viral hemagglutinin of H1 and H5 subtypes and protect mice from lethal disease. The use of luciferase reporter influenza viruses allows for new mechanistic studies to expand our knowledge of virus-induced disease and provides a new quantitative method to evaluate future antiviral therapies.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, New York, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Heaton
authors.forename: Victor H
authors.initials: VH
authors.lastname: Leyva-Grado
authors.forename: Gene S
authors.initials: GS
authors.lastname: Tan
authors.forename: Dirk
authors.initials: D
authors.lastname: Eggink
authors.forename: Rong
authors.initials: R
authors.lastname: Hai
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D017930:Genes, Reporter; D009980:Influenza A virus / Q000235:genetics / Q000472:pathogenicity*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology*; D013194:Staining and Labeling / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D008156:Luciferases