title: The first autopsy case of pandemic influenza (A/H1N1pdm) virus infection in Japan: detection of a high copy number of the virus in type II alveolar epithelial cells by pathological and virological examination.
abstract: We report the pathological and virological findings of the first autopsy case of the 2009 pandemic influenza (A/H1N1pdm) virus infection in Japan. A man aged 33 years with chronic heart failure due to dilated cardiomyopathy, mild diabetes mellitus, atopic dermatitis, bronchial asthma, and obesity died of respiratory failure and multiple organ dysfunction syndrome. Macroscopic examination showed severe pulmonary edema and microscopically the lung sections showed very early exudative-stage diffuse alveolar damage (DAD). Immunohistochemistry revealed proliferation of the influenza (A/H1N1pdm) virus in alveolar epithelial cells, some of which expressed SAalpha2-3Gal on the cell surface. Influenza (A/H1N1pdm) virus genomic RNA and mRNA were also detected in alveolar epithelial cells. Real-time PCR revealed 723 copies/cell in the left lower lung section from which the influenza (A/H1N1pdm) virus was isolated. Electron microscopic analysis revealed filamentous viral particles in the lung tissue. The concentrations of various cytokines/chemokines in the serum and the autopsied lung tissue were measured. IL-2R, IL-6, IL-8, IL-10, IFN-alpha, MCP-1, and MIG levels were elevated in both. These findings indicated a case of viral pneumonia caused by influenza (A/H1N1pdm) virus infection, showing characteristic pathological findings of the early stage of DAD.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakajima
authors.forename: Satoru
authors.initials: S
authors.lastname: Hata
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Tobiume
authors.forename: Harutaka
authors.initials: H
authors.lastname: Katano
authors.forename: Keiko
authors.initials: K
authors.lastname: Kaneko
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Michiyo
authors.initials: M
authors.lastname: Kataoka
authors.forename: Akira
authors.initials: A
authors.lastname: Ainai
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.forename: Tamami
authors.initials: T
authors.lastname: Odai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Urasawa
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Ogino
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Masahide
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
mesh_terms: D000328:Adult; D001344:Autopsy; D016207:Cytokines / Q000032:analysis / Q000097:blood; D004847:Epithelial Cells / Q000821:virology*; D017809:Fatal Outcome; D006801:Humans; D007150:Immunohistochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification*; D007251:Influenza, Human / Q000150:complications / Q000175:diagnosis* / Q000821:virology*; D007564:Japan; D008168:Lung / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008297:Male; D008853:Microscopy; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D011650:Pulmonary Alveoli / Q000821:virology*; D012131:Respiratory Insufficiency; D019562:Viral Load
chemical_list: D016207:Cytokines