title: Local innate immune responses and influenza virus transmission and virulence in ferrets.
abstract: Host innate immunity is the first line of defense against invading pathogens, including influenza viruses. Ferrets are well recognized as the best model of influenza virus pathogenesis and transmission, but little is known about the innate immune response of ferrets after infection with this virus. The goal of this study was to investigate the contribution of localized host responses to influenza virus pathogenicity and transmissibility in this model by measuring the level of messenger RNA expression of 12 cytokines and chemokines in the upper and lower respiratory tracts of ferrets infected with H5N1, H1N1, or H3N2 influenza viruses that exhibit diverse virulence and transmissibility in ferrets. We found a strong temporal correlation between inflammatory mediators and the kinetics and frequency of transmission, clinical signs associated with transmission, peak virus shedding, and virulence. Our findings point to a link between localized innate immunity and influenza virus transmission and disease progression.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. ttumpey@cdc.gov
authors.forename: Taronna R
authors.initials: TR
authors.lastname: Maines
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Belser
authors.forename: Kortney M
authors.initials: KM
authors.lastname: Gustin
authors.forename: Neal
authors.initials: N
authors.lastname: van Hoeven
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.forename: Nicholas
authors.initials: N
authors.lastname: Svitek
authors.forename: Veronika
authors.initials: V
authors.lastname: von Messling
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005289:Ferrets; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D008297:Male; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000635:transmission* / Q000821:virology; D012137:Respiratory System / Q000276:immunology / Q000821:virology; D014774:Virulence; D017201:Virus Shedding
chemical_list: D016207:Cytokines