title: Oseltamivir inhibits influenza virus replication and transmission following ocular-only aerosol inoculation of ferrets.
abstract: Ocular exposure to influenza virus represents an alternate route of virus entry capable of establishing a respiratory infection in mammals, but the effectiveness of currently available antiviral treatments to limit virus replication within ocular tissue or inhibit virus spread from ocular sites to the respiratory tract is poorly understood. Using an inoculation method that delivers an aerosol inoculum exclusively to the ocular surface, we demonstrate that oral oseltamivir administration following ocular-only aerosol inoculation with multiple avian and human influenza viruses protected ferrets from a fatal and systemic infection, reduced clinical signs and symptoms of illness, and decreased virus transmissibility to susceptible contacts when a respiratory infection was initiated. The presence of oseltamivir further inhibited influenza virus replication in primary human corneal epithelial cells. These findings provide critical experimental evidence supporting the use of neuraminidase inhibitors during outbreaks of influenza virus resulting in ocular disease or following ocular exposure.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. Electronic address: jax6@cdc.gov.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Belser
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Taronna R
authors.initials: TR
authors.lastname: Maines
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA; Microbiology and Molecular Genetics Graduate Program, Emory University, Atlanta, GA, USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Creager
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005289:Ferrets; D008297:Male; D009975:Orthomyxoviridae / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D053139:Oseltamivir / Q000008:administration & dosage*; D016019:Survival Analysis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir
keywords: Aerosol; Antiviral; Ferret model; Influenza virus; Oseltamivir (Tamiflu); Transmission