title: Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan.
abstract: This article describes the pathological studies of fatal severe acute respiratory syndrome (SARS) in a 73-year-old man during an outbreak of SARS in Taiwan, 2003. Eight days before onset of symptoms, he visited a municipal hospital that was later identified as the epicenter of a large outbreak of SARS. On admission to National Taiwan University Hospital in Taipei, the patient experienced chest tightness, progressive dyspnea, and low-grade fever. His condition rapidly deteriorated with increasing respiratory difficulty, and he died 7 days after admission. The most prominent histopathologic finding was diffuse alveolar damage of the lung. Immunohistochemical and in situ hybridization assays demonstrated evidence of SARS-associated coronavirus (SARS-CoV) infection in various respiratory epithelial cells, predominantly type II pneumocytes, and in alveolar macrophages in the lung. Electron microscopic examination also revealed coronavirus particles in the pneumocytes, and their identity was confirmed as SARS-CoV by immunogold labeling electron microscopy. This report is the first to describe the cellular localization of SARS-CoV in human lung tissue by using a combination of immunohistochemistry, double-stain immunohistochemistry, in situ hybridization, electron microscopy, and immunogold labeling electron microscopy. These techniques represent valuable laboratory diagnostic modalities and provide insights into the pathogenesis of this emerging infection.
authors.affiliation: Infectious Disease Pathology Activity, Division of Viral and Rickettsial Diseases, Center for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Wun-Ju
authors.initials: WJ
authors.lastname: Shieh
authors.forename: Cheng-Hsiang
authors.initials: CH
authors.lastname: Hsiao
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Paddock
authors.forename: Jeannette
authors.initials: J
authors.lastname: Guarner
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Goldsmith
authors.forename: Kathleen
authors.initials: K
authors.lastname: Tatti
authors.forename: Michelle
authors.initials: M
authors.lastname: Packard
authors.forename: Laurie
authors.initials: L
authors.lastname: Mueller
authors.forename: Mu-Zong
authors.initials: MZ
authors.lastname: Wu
authors.forename: Pierre
authors.initials: P
authors.lastname: Rollin
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
mesh_terms: D000368:Aged; D000956:Antigens, Viral / Q000032:analysis; D002462:Cell Membrane / Q000821:virology; D003593:Cytoplasm / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D017809:Fatal Outcome; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D002479:Inclusion Bodies / Q000821:virology; D008168:Lung / Q000648:ultrastructure / Q000821:virology*; D016676:Macrophages, Alveolar / Q000821:virology; D008297:Male; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D045169:Severe Acute Respiratory Syndrome / Q000473:pathology / Q000821:virology*; D013624:Taiwan
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral