title: Rapid control of pandemic H1N1 influenza by targeting NKT-cells.
abstract: Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses. We show that intranasal but not systemic administration of α-GalCer to piglets infected with pandemic A/California/04/2009 (CA04) H1N1 IAV ameliorated disease symptoms and resulted in the restoration of weight gain to the level of uninfected pigs. Correspondingly, viral titers in the upper-and lower-respiratory tract were reduced only in piglets that had received intranasal α-GalCer. Most significantly, lung inflammation as a consequence of virus persistence was largely prevented when NKT-cells were targeted via the respiratory route. Thus, targeting mucosal NKT-cells may provide a novel and potent platform for improving the course of disease in swine infected with seasonal and pandemic influenza viruses, and leads to the suggestion that this may also be true in humans and therefore deserves further study.
authors.affiliation: Department of Animal Science, University of Florida, Gainesville, FL, USA.
authors.forename: Bianca L
authors.initials: BL
authors.lastname: Artiaga
authors.affiliation: Department of Animal Science, University of Florida, Gainesville, FL, USA.
authors.forename: Guan
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Tarun E
authors.initials: TE
authors.lastname: Hutchinson
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Loeb
authors.affiliation: Diagnostic Medicine and Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Richt
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.|Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Lednicky
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.affiliation: Department of Animal Science, University of Florida, Gainesville, FL, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Driver
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005699:Galactosylceramides / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D013552:Swine; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D005699:Galactosylceramides; C493154:alpha-galactosylceramide