title: Protection of ferrets from pulmonary injury due to H1N1 2009 influenza virus infection: immunopathology tractable by sphingosine-1-phosphate 1 receptor agonist therapy.
abstract: Influenza infection of humans remains an important public health problem. Vaccine strategies result in a significant but only partial control (65-85%) of infection. Thus, chemotherapeutic approaches are needed to provide a solution both for vaccine failures and to limit infection in the unvaccinated population. Previously (Walsh et al., 2011; Teijaro et al., 2011) documented that sphingosine-1-phosphate 1 receptor (S1P1R) agonists significantly protected mice against pathogenic H1N1 influenza virus by limiting immunopathologic damage while allowing host control of the infection. Here we extend that observation by documenting S1P1R agonist can control pathogenic H1N1 influenza infection in ferrets. S1P1R agonist was more effective in reducing pulmonary injury than the antiviral drug oseltamivir but, importantly, combined therapy was significantly more effective than either therapy alone.
authors.affiliation: Viral-Immunobiology Laboratory, Department of Immunology & Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: teijaro@scripps.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Teijaro
authors.affiliation: Viral-Immunobiology Laboratory, Department of Immunology & Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: walshk6@gene.com.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Walsh
authors.affiliation: Battelle, 505 King Avenue, Columbus, OH 43201, USA. Electronic address: longj@battelle.org.
authors.forename: James P
authors.initials: JP
authors.lastname: Long
authors.affiliation: Battelle, 505 King Avenue, Columbus, OH 43201, USA. Electronic address: tordoffk@battelle.org.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Tordoff
authors.affiliation: Battelle, 505 King Avenue, Columbus, OH 43201, USA. Electronic address: starkg@battelle.org.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Stark
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI 53711, USA. Electronic address: aefenney@vetmed.wisc.edu.
authors.forename: Amie J
authors.initials: AJ
authors.lastname: Eisfeld
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI 53711, USA; Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; ERATO Infection-Induced Host Response Project, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI 53706, USA. Electronic address: kawaokay@svm.vetmed.wisc.edu.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.affiliation: Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Scripps Research Institute Molecular Screening Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: hrosen@scripps.edu.
authors.forename: Hugh
authors.initials: H
authors.lastname: Rosen
authors.affiliation: Viral-Immunobiology Laboratory, Department of Immunology & Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: mbaobo@scripps.edu.
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005289:Ferrets; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors
keywords: Ferrets; H1N1 influenza; Oseltamivir; Pathogenesis; RP-002; S1P1 Rec agonist