title: Antibody to severe acute respiratory syndrome (SARS)-associated coronavirus spike protein domain 2 cross-reacts with lung epithelial cells and causes cytotoxicity.
abstract: Both viral effect and immune-mediated mechanism are involved in the pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In this study, we showed that in SARS patient sera there were autoantibodies (autoAbs) that reacted with A549 cells, the type-2 pneumocytes, and that these autoAbs were mainly IgG. The autoAbs were detectable 20 days after fever onset. Tests of non-SARS-pneumonia patients did not show the same autoAb production as in SARS patients. After sera IgG bound to A549 cells, cytotoxicity was induced. Cell cytotoxicity and the anti-epithelial cell IgG level were positively correlated. Preabsorption and binding assays indicated the existence of cross-reactive epitopes on SARS-CoV spike protein domain 2 (S2). Furthermore, treatment of A549 cells with anti-S2 Abs and IFN-gamma resulted in an increase in the adherence of human peripheral blood mononuclear cells to these epithelial cells. Taken together, we have demonstrated that the anti-S2 Abs in SARS patient sera cause cytotoxic injury as well as enhance immune cell adhesion to epithelial cells. The onset of autoimmune responses in SARS-CoV infection may be implicated in SARS pathogenesis.
authors.affiliation: Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lin
authors.forename: C F
authors.initials: CF
authors.lastname: Lin
authors.forename: Y T
authors.initials: YT
authors.lastname: Fang
authors.forename: Y M
authors.initials: YM
authors.lastname: Kuo
authors.forename: P C
authors.initials: PC
authors.lastname: Liao
authors.forename: T M
authors.initials: TM
authors.lastname: Yeh
authors.forename: K Y
authors.initials: KY
authors.lastname: Hwa
authors.forename: C C K
authors.initials: CC
authors.lastname: Shieh
authors.forename: J H
authors.initials: JH
authors.lastname: Yen
authors.forename: H J
authors.initials: HJ
authors.lastname: Wang
authors.forename: I J
authors.initials: IJ
authors.lastname: Su
authors.forename: H Y
authors.initials: HY
authors.lastname: Lei
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D002448:Cell Adhesion; D016923:Cell Death; D045744:Cell Line, Tumor; D003429:Cross Reactions / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D045473:Severe acute respiratory syndrome-related coronavirus; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000473:pathology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins