title: Systemic dissemination of H5N1 influenza A viruses in ferrets and hamsters after direct intragastric inoculation.
abstract: Although oral exposure to H5N1 highly pathogenic avian influenza viruses is a risk factor for infection in humans, it is unclear how oral exposure to these virus results in lethal respiratory infections. To address this issue, we inoculated ferrets and hamsters with two highly pathogenic H5N1 strains. These viruses, inoculated directly into the stomach, were isolated from the large intestine and the mesenteric lymph nodes within 1 day of inoculation and subsequently spread to multiple tissues, including lung, liver, and brain. Histopathologic analysis of ferrets infected with virus via direct intragastric inoculation revealed lymph folliculitis in the digestive tract and mesenteric lymph nodes and focal interstitial pneumonia. Comparable results were obtained with the hamster model. We conclude that, in mammals, ingested H5N1 influenza viruses can disseminate to nondigestive organs, possibly through the lymphatic system of the gastrointestinal tract.
authors.affiliation: Division of Zoonosis, Department of Microbiology and Infection, Graduate School of Medicine, Kobe University, Hyogo 650-0017, Japan. kyoko.tanaka@aioros.ocn.ne.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.forename: Akiko
authors.initials: A
authors.lastname: Makino
authors.forename: Hiroji
authors.initials: H
authors.lastname: Tanaka
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Mai Q
authors.initials: MQ
authors.lastname: Le
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Imai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000825:Animal Structures / Q000473:pathology / Q000821:virology; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D005751:Gastric Lavage; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D008647:Mesocricetus; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology*; D012376:Rodent Diseases / Q000473:pathology* / Q000821:virology*; D013997:Time Factors